2019 -
Emmett Cunningham, Jr., M.D., Ph.D., M.P.H. Senior Managing Director Blackstone Life Sciences
HEATHEGY TEAM
CRAIG SIMAK
CRAIG SIMAK DANIELLE SILVA MAUREEN LINNEMANN 1200 OIS@AAO 24 Meetings > 1,150 1000 ~ 13,500 Attendees
800 OIS@ASCRS 600 > 650
400 OIS@ASRS 200 > 300
0 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 2020 Registrants 3% 10% OIS@AAO 2019 ( > 1,150) 8% Academia, Government, or Association 41% Adviser, Consultant, or Service Provider Finance/Investment Firm Large Multi-National Corporation Physician/Healthcare Provider 25% Press/Media Start-up/Emerging Growth Company 3% 25 Countries 10% 32 US States
Record Number of CDER NME NDA/BLA Approvals in 2018
70 BLA 59 60 NDA
50 45 46 Number 39 41 of 40 35 36 Drugs 30 30 30 27 27 24 26 22 24 21 20 21 22 20 17 18
10
0 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 Source: FDA 1998 - 2018 High Innovation Record Number of • 31 (53%) Orphan CDER NME NDA/BLA Approvals in 2018 • 26 (44%) Priority Review
• 16 (27%) Fast Track
• 12 (20%) Break Through Designation 59 • 18 (30%) Oncology • 1 (0%) Ophthalmology Cenegermin-bkbj Ophthalmic Solution, (OXERVATE®) Ophthalmic Drugs Streamlined Reporting of Ophthalmology Clinical Group
CDER As of January, 2018 Ophthalmology Clinical Group Reported Directly & Independently to Deputy Director Office of New Drugs Peter Stein, MD
Five Additional Office of Offices of Drug Antimicrobial Evaluation (ODEs) Products
Division of Division of Division of Transplant and Anti-Infective Anti-Viral Ophthalmology Products Products Dr. Wiley A. Chambers Products Supervisory Medical Officer Division of Transplant and Ophthalmology Products (DTOP) Re-Org Officially Approved September 26, 2019
https://www.fda.gov/drugs/regulatory-science-research-and-education/reorganization-office-new-drugs-corresponding-changes-office-translational-sciences-and-office Original NDA/BLA Approvals – 1988 to 2019 Center for Drug Evaluation and Research 2019
160 129 140
120
100
80
60 • Range: 0 – 9 • Mean: 4.4 40 Ophthalmic / Year • Median: 4
20 7 0 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Ophthalmic Approvals Total Approvals Linear (Ophthalmic Approvals) Linear (Total Approvals) Data provided by : Wiley A. Chambers, MD Gary Novack, PhD Supervisory Medical Officer Pharma . Logic Consulting, Inc. Division of Transplant and Ophthalmology Products Original NDA/BLA Approvals Center for Drug Evaluation and Research - FY2019 140 7 5.4% Ophthalmic 122 October 1, 2018 thru September 30, 2019 120 • Fluocinolonide acetonide intravitreal implant (YUTIQ®), 0.18mg, a corticosteroid implant indicated for the treatment of chronic non-infectious uveitis affecting the posterior segment of the eye, October 12, 2018 (NDA) – Eyepoint 100 Pharmaceuticals, Inc. •Dexamethasone Ophthalmic Insert (DEXTENZA®), 0.4mg, a corticosteroid insert indicated for the treatment of ocular pain associated with ophthalmic surgery. November 30, 2018 (NDA) – Ocular Therapeutix, Inc. 80 •Loteprednol etabonate ophthalmic gel (LOTEMAX SM®), 0.38% in new formulation to treat post-operative inflammation and pain following ocular surgery, February 22, 2019 (NDA) – Bausch & Lomb, Inc. • Tetracaine hydrochloride ophthalmic solution, 0.5% , local ophthalmic anesthetic – March 12, 2019 (NDA) – 60 Bausch & Lomb, Inc. • Netarsudil / Latanoprost (ROCKLATAN®), 0.02%/0.005%, fixed dose combination for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension, March 12, 2019 (NDA) – Aerie 40 Pharmaceuticals, Inc. • Acyclovir Ophthalmic Ointment (AVACLYR®), 3.0%, indicated for the treatment of acute herpetic keratitis (dendritic ulcers) in patients with herpes simplex (HSV-1 and HSV-2) virus, March 29, 2019 (NDA) – Fera Pharmaceuticals, LLC. 20 •Brolucizumab (Beovu®), 6mg/0.05mg, indicated for the treatment of wet age-related macular degeneration, October 8, 2019, Novartis AG 0 Ophthalmic Non-Ophthalmic Data provided by : Wiley A. Chambers, MD Gary Novack, PhD Supervisory Medical Officer Pharma . Logic Consulting, Inc. Division of Transplant and Ophthalmology Products FDA Approved October 12, 2018
YUTIQTM SHAM Fluocinolone acetonide intravitreal implant, 0.18 mg (YUTIQ™), contains a corticosteroid and is indicated for the Fluocinolone Acetonide treatment of chronic non-infectious uveitis affecting the Intravitreal Implant posterior segment of the eye. FDA Approved November 30, 2018
First FDA Approved Punctal Plug Delivery System
Dexamethasone Ophthalmic Insert (DEXTENZA®), 0.4mg A corticosteroid insert indicated for the treatment of ocular pain associated with ophthalmic surgery. November 30, 2018 (NDA) FDA Approved February 22, 2019
Proportion of Patients with Complete Resolution of ACC at Day 8 (Pooled Analysis)
60% LOTEMAX® SM (n=371)
P<0. 40% 0001 30%
20% 15%
0% Day 8 Loteprednol etabonate ophthalmic gel (LOTEMAX SM®), 0.38% in new formulation to treat post-operative inflammation and pain following ocular surgery FDA Approved - March 12, 2019 Launched – May, 2019
First Fixed-Dose Combination Containing a PGA
First Once-Daily Fixed-Dose Combination
Netarsudil / Latanoprost (ROCKLATAN®), 0.02%/0.005%, is a fixed-dose combination indicated for the reduction of elevated intraocular pressure in patients with open-angle glaucoma or ocular hypertension “Beovu® is the first to offer less frequent dosing in the first year of therapy while maintaining its effectiveness.”
October 8, 2019
Brolucizumab (Beovu®), 6mg/0.05mg “More than half of patients on brolucizumab (56% indicated for the treatment of wet in HAWK, 51% in HARRIER) age-related macular degeneration were able to maintain a 3-month dosing interval” Number of CDER NME NDA/BLA Approvals, 2015-2019*
59 60 All Indications 60 Ophthalmology
50 50 45 46
40 40
30 30 30 22 20 20
10 10 3 0 1 1 1 0 0 2015 2016 2017 2018 2019* 2015 2016 2017 2018 2019*
* 2019 Through October 8, 2019; FDA Global Ophthalmic Pharmaceutical Market Revenues by Specialty
50 Total ($B) 42.14
40 6.9 Total ($B) 29.04 6.5 30 6.2 6.3 20 4.9 Revenues ($B) Revenues 4.9 Anti-VEGF 10 22.4 13.0 Largest
0 2019 2024 IVT Anti-VEGF (AMD, DME, RVO, Etc.) Glaucoma Pharmaceuticals Dry Eye All Other
Source: Market Scope Estimates 2019; Courtesy Market Scope. http://market-scope.com/ Market Scope ® IVT Injections….
Courtesy Dr. Peter Karth and Dr. Marc Blumenkranz Global Anti-VEGF Injections (M) Global 25 24.4M
20 Ex-US 17.5M 15
10
IVT Injections Injections IVT (M) US 5 6.9M
0 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 United States Outside United States Global
Source: Market Scope Estimates 2019; Courtesy Market Scope. http://market-scope.com/ Market Scope ® Wet AMD OPT-302-1002 – Mean Change in VA Over Time
Additive benefit of OPT-302 evident from 8-weeks Mean Gains in Visual Acuity From Baseline Benefit of Pan-VEGF Inhibition (A + C + D) +14.2 *p = 0.0107 +10.8 +9.4
Sham + Lucentis® (0.5 mg) OPT-302 (0.5 mg) + Lucentis® (0.5 mg) OPT-302 (2.0 mg) + Lucentis® (0.5 mg) (n = 119) (n = 122) (n = 121)
OPT-302-1002 clinical trial (NCT03345082). Graph represents observed data and standard error of the mean (SEM). Modified Intent-to-treat study population. BCVA, Best Corrected Visual Acuity; ETDRS, Early Treatment Diabetic Retinopathy Study. * Difference in Least Square Means, using Model for Repeated Measures (MRM) analysis. Control of Type I error via the Hochberg Procedure. GB-102 – Small Molecule TKI (Sunitinib – Pan VEGFR Antagonist)
• Best performing dose • ~90% of patients rescue-free at 6 Months • ~60% of patients rescue-free at 8 months
• Excellent safety profile
• Phase 2a in Macular Edema Q3 2019
• Phase 2b in wAMD Q3 2019 Antibody Biopolymer Conjugates (ABCs): a new scientific design platform for extended durability intravitreal therapeutics
• Phase 1 Data: 110+ Patients: wAMD, DME (NPDR, PDR), RVO • Safety: 300+ injections: no inflammation or other safety signals • Efficacy: strong anti-VEGF efficacy in each indication • Durability: wAMD dosing interval of 3-5 months in emerging data (Retina Society)
KSI-301: anti- VEGF ABC Antibody and optically clear, branched, high molecular weight phosphorylcholine biopolymer covalently bound via single, site- specific stable linkage • New durability data in wAMD, DME, and RVO to be presented Friday 10/11 at AAO • Pivotal ‘DAZZLE’ wAMD study: KSI-301 q3-5 month vs Eylea q2mo now enrolling OPTIC Cohort 1 24-week conclusions
ADVM-022 AAV.7m8 capsid • Zero rescue injections required • Consistent and sustained anatomical improvements on OCT ITR C11 aflibercept ITR Aflibercept expression cassette • BCVA stability maintained
RN • ADVM-022 - safe and well tolerated A Aflibercept
Day -14 to -7: Day 1: 24-week safety and 52-week safety and aflibercept ADVM-022 efficacy assessment efficacy assessment
Baseline assessment Treatment evaluation Treatment evaluation Follow-up
Weeks: 4 8 12 16 20 24 52 104
Rescue at any time if disease activity meets retreatment criteria† Sub – Retinal Delivery REGENXBIO ANNOUNCES EXCLUSIVE WORLDWIDE OPTION AND LICENSE AGREEMENT WITH CLEARSIDE BIOMEDICAL FOR EVALUATION OF IN- OFFICE DELIVERY PLATFORM FOR RGX-314 Ophthalmic Devices 510(k) Clearances Division of Ophthalmic and Ear, Nose and Throat Devices - FY2018 3000 2.2% of Total 2500 2348 54
2000
1500
1000 Ophthalmic
500 Non-Ophthalmic
0
Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc. PMA Approvals – 2004 to 2019 Division of Ophthalmic and Ear, Nose and Throat Devices 80 2019 70
60
50 49 40
30
20
10 3 0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Opthalmic PMA Total PMA
Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc. PMA Approvals Division of Ophthalmic and Ear, Nose and Throat Devices- FY2018 60 5.8% of Total 3 50 49
40 October 1, 2018 thru September 30, 2019 • Visumax Femtosecond Laser, Carl Zeiss Meditec, Inc. October 4, 2018.
30 • Acrysof Iq Panoptix Trifocal Intraocular Lens, Alcon Research, Ltd. August 28, 2019. • Star S4 Excimer Laser System and Idesign Refractive Studio, AMO 20 Manufacturing USA, LLC, September 9, 2019
10 Ophthalmic Non-Ophthalmic 0
Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc. De Novo Approvals – 2004 to 2018 Center for Devices and Radiological Health 2 Eye 45 2018
40 De Novo Approvals “A regulatory pathway for some low- to moderate-risk medical devices that are 35 not substantially equivalent to an already legally-marketed device.” 3 Eye 2016 2019 30 29 Total 25
20 0 Eye 1 Eye 1 Eye 2019 15 2011 2017 10 1 Eye 2015 5
0 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 de novo 510(k) Data Provided by: Lee Kramm, MD, MSE & Judy Gordon, DVM ClinReg Consulting Services, Inc. Global Ophthalmic Procedures - 2019 (69.5 Million - Up 2.3 % from 2018)
IVT Injections (23.6M) 35%
Laser Refractive (4.2M) 6%
Laser Photocoagulation (1.7M) 3%
Vitrectomies (1.8M) 3%
Glaucoma Laser (2.3M) Cataract, RLE, 3% Phakic IOLs Glaucoma Filtering, Shunts, (29.5M) etc. (0.9M) 43% All Other 1% (4.4M)… XPORT Lens Fragmentation System FDA Apporved August 13, 2019
ZEISS miLOOP Lens fragmentation device PMA Approvals 2018 / 2019
Visumax Femtosecond Laser Star S4 Excimer Laser System and Carl Zeiss Meditec, Inc Acrysof Iq Panoptix Trifocal Intraocular Lens iDesign Refractive Studio Alcon Research, Ltd AMO Manufacturing USA, LLC, “91.8% of RxLAL eyes achieved result within 0.50 D of target MRSE (similar to LASIK results)
• FDA Approved – November 22, 2017 • Premium IOL designation
• EU Approved
• 15 commercial customers & growing
Light Adjustable Lens (LAL)
Light Delivery Device (LDD) Funding NEI Funding Up Modestly, Both Actual and to 1999 Buying Power ($000) $900,000
$800,000 $793M $700,000
$600,000
$500,000 $437M $400,000
$300,000
$200,000
$100,000
$- 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 NEI Operating Budget 395, 450, 510, 580, 633, 653, 669, 666, 666, 667, 688, 707, 700, 702, 657, 675, 676, 707, 731, 770, 793, Buying Power 395, 434, 476, 524, 552, 549, 542, 516, 497, 475, 476, 475, 458, 453, 416, 418, 411, 420, 424, 435, 437,
Data provided by : Mala Dutta, Ph.D. Office of Translational Research, NEI Total Venture Capital (All Rounds) Invested Over Time 16 $14.0Bn
14 * Biotech Medtech Biotech Strong 12 Medtech Flat 10
8
Billions ($) Billions 6 $3.1Bn 4 * 2
0
* Adjusted for the full year based on actual data from the first three quarters of 2018. Private Biotech / Device / Dx / Tools Venture Capital ($Bn) 30 Raised vs Total Invested ($Bn) - 2005 to 2019*
25 $24.2Bn
VC Fundraised Total Invested 20 Non-VC Investors Increasingly Important 15 Crossover Hedge Funds Strategics 10 $11.6Bn 5
0 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019
Source: PricewaterhouseCoopers, Silicon Valley Bank *2019 extrapolated from 1H2019 Courtesy Jon Norris Ophthalmic Investments Over Time (1999 – 2019*) Total Dollars Number of Invested ($M) Deals
1600 $1.5Bn! 40 Ophthalmology 1400 35 VC Funding and Number of Deals 1200 30 Record Year @ > $1.5Bn 1000 25
800 20
600 15
400 10
200 5
0 0 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 # Rx Deals # Device Deals VC Investment ($USD, Millions)
*2019 through early October. Source: Strategic Transactions | Pharma Intelligence, 2019 US Biotech Series A Investments* By Indications – 2009 through 2018
Oncology 187 Neurology 80 Orphan/Rare 59 Anti-Infectives 37 Greatest Growth LTM Auto-Immune 33 1. Oncology: 56 new Metabolic 25 2. Neurology: 27 new Ophthalmology 24 3. Orphan / Rare: 20 new 4. Anti-infective: 9 new Asthetics/Dermatology 29 5. Auto-Immune: 6 new Gastroenterology 14 6. Ophthalmology: 3 new Cardiology 14
0 20 40 60 80 100 120 140 160 180 200 * > $2M Number of Series A Deals Courtesy Jon Norris US Device Series A Investments* By Indications – 2009 to 1H2019
Neurology 63
Surgical 62
Cardiology 62
Respiratory 61
Orthopedic 52 Greatest Growth LTM 1. Orthopedic: 11 new Vascular 37 2. Cardiology: 6 new Ophthalmology 29 3. Surgical: 6 new 4. Neurology: 5 new Urology/Gynecology 13 5. Respiratory: 4 new Asthetics/Dermatology 11 6. Ophthalmology: 2 new
0 10 20 30 40 50 60 70 Number of Series A Deals * > $2M Courtesy Jon Norris
OIS Index Components
Ticker Mkt Cap Ticker Mkt Cap Alcon ALC $28,330 NicOx NXOA.F $170 • 35 Companies Cooper Companies COO $14,700 Aldeyra Therapeutics ALDX $145 • 89% Device Carl Zeiss Meditec AFX.F $10,750 Harrow Health HROW $140 Bausch Health BHC $7,700 Ocular Therapeutix OCUL $130 • 11% Biopharma Glaukos GKOS $2,275 Kala Pharmaceuticals KALA $130 • $73.3Bn Total Valuation Apellis Pharma APLS $1,350 Oxurion OXUR.BR $105 • Median Market Cap $192M REGENXBIO RGNX $1,300 Second Sight EYES $80 (Range $12M - $28.3Bn) STAAR Surgical STAA $1,150 AGTC AGTC $75 Aerie Pharma AERI $880 Ellex Medical Lasers ELX.AX $55 Omeros OMER $800 IVERIC bio ISEE $45 Opthea OPT.AX $585 Eyenovia EYEN $45 MeiraGTx MGTX $530 Alimera Sciences ALIM $40 Avedro AVDR $390 GenSight Biologics SIGHT.PA $40 Adverum Biotech ADVM $350 Aerpio Pharma. ARPO $30 Molecular Partners MOLN.SW $300 Iridex IRIX $25 Unity Biotechnology UBX $260 Clearside Bio CLSD $25 KalVista Pharma. KALV $200 NovaBay Pharma NBY $12 EyePoint Pharma. EYPT $190 *October 1, 2019 Courtesy Michael Lachman Biotech Stock Index (NBI) Down 4,500 2008 4,000
3,500
3,000
2,500
2,000
1,500
1,000
500
0 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 2019 Courtesy Michael Lachman Biotech Stock Index (NBI) Down (-18.5%) 115
110
105
100 NASDAQ Biotechnology Index 95
90
85
80
75
70
65
Courtesy Michael Lachman US Medical Device Index Steadily Up (+8.7%) 115
110
105
100
95
90 US Medical Devices Index
85
80
75
70
65
Courtesy Michael Lachman 115 OIS Index Down Since Q2-2019 (-13.0%)
110
105
100
95
90
85
80
75
70
65
Courtesy Michael Lachman Relative Performance of Indices 115
110 US Medical Devices Index 105
100
95
90
85
80 NASDAQ 75 Biotechnology Index
70
65
Courtesy Michael Lachman
Top Exits by Indication 2014 - 1H2019 90
80
70 23
60
50
40 12 12 30 62 6 3 20 3 31 30 10 27 17 12 0 Oncology Orphan/Rare Neurology Platform Anti-Infective Ophthalmology IPO M & A Courtesy Jon Norris
OPHTHALMOLOGY FINANCING ACTIVITY
$82M $75M $71M FOs $72M $3M $20M $28M $14M $365M
Sep 18 Dec 18 Mar 19 Jun 19 Sep 19
IPOs $398M $22M $23M
$94M $54M $85M $120M
Marquee M&A $4,851M $877M $5.7Bn
Source: Company filings and Factset Research Systems as of 9/30/2019 Courtesy Andrew Gitkin and Kyle Madan, Raymond James57 Note: Includes equity and marquee M&A events from 09/26/2018 to 09/30/2019
Economic Indicators Stable But Uncertain
Positives Negatives • Interest Rates Low Globally • Peak Multiples • Record Low Unemployment • Global Political Upheavals • Resilient Public Markets • International Economic Doubt • Substantial Capital Available • Search for Yield – Anywhere Courtesy Andrew Gitkin, Raymond James Not ‘If,’ but ‘When?’ Yield Curve Spread Has Dropped to Zero
Yield Curve Spread 3.5 Recession Inversion 3.0 Pre-dates Recession
2.5
2.0
1.5 Inversion Inversion 1.0
0.5
0.0
-0.5
-1.0
Yield Curve Spread, Q3-1993 – Q3-2019 Market Yield on U.S. Treasury Securities, 10-yr – 2 yr Spread Data from US Federal Reserve
Courtesy Michael Lachman, EyeQ Research
Trump announces plan to lower drug prices:
"This is a total rip off, and we are ending it"
https://www.cbsnews.com/news/trump-prescription-drug-prices-plan-announcement-2018-05-11/ October 4, 2020 64 Mergers & Acquisitions Medtech and Biotech M&A Activity Over the Last 10 Years
70
59 60 55 55 53 52 51 48 48 50 45
40 31 30 25 30 28 29 25 20 22 23 23 20 19 17 16 10
0 2009 2010 2011 2012 2013 2014 2015 2016 2017 2018 YTD 2019 Biotech Medtech
Includes Acquisitions with disclosed transaction values over $50M Courtesy of Udit Patel, Piper Jaffray Biopharma Ophthalmology M&A Activity Continues to be Robust
$84Bn $5.3Bn ND (Xiidra)
ND $800M
$4.8Bn* $25M $12M
All deals since October 2018 Note: ND stands for Not Disclosed *Announced, not closed Courtesy of Udit Patel, Piper Jaffray Device Ophthalmology M&A Activity Continues to be Robust
ND $500M $46M ND
$285M $485M ND $157M
ND ND ND ND
ND ND $170M ND
All deals since October 2018 Note: ND stands for Not Disclosed Courtesy of Udit Patel, Piper Jaffray Private Company Acquisitions – 2005 – 3Q2019 Most Structured – Device and Biopharma
Device - All Companies Biopharma - All Companies 100% 100% 90% 90% 82% 80% 80% 70% 64% 70% 60% 60% 50% 50% 40% 40% 30% 30% 20% 20% 10% 10% 0% 0%
Private M&A Bio ($75M+ Upfront) and Device ($50M+ Upfront) Courtesy Jon Norris Mega Deals
$84Bn $62Bn Good for Abbvie Good for Novartis (Xiidra) ?Impact on ?Bad for Ophthalmology? Ophthalmology?
Save the Dates
nd th th 2 Annual OIS Optometry 9 Annual OIS Anterior 5 Annual OIS Retina 12th Annual OIS Atlanta, GA Boston, MA Seattle, WA Las Vegas March 4, 2020 May 14, 2020 July 23, 2020 November 12, 2020
OIS: The Group for Ophthalmology @OISTWEETS #OISAAO /OIS.NET Innovation & Investment Backup Slides Ophthalmology Focused Funds
• Curt LaBelle, Sean Ianchulev - Managing Partners • E-mail: [email protected] • Ophthalmology + - Device, Drugs • Investment Size: $2M - $8M • Seed to Human POC (4 year horizon) • Bill Link, Andy Corley, Dick Lindstrom - • www.privatemedicalequity.com Managing Partners • E-mail: [email protected] • Ophthalmology+ - Device, Drugs, Drug Delivery • Investment Size: $10 - $30M • Angela MacFarlane & Eugene DeJuan - Managing Partners • Mid to Late Stage • E-mail: [email protected]; [email protected] • www.flyinglpartners.com • Mark Blumenkranz – Founder and Managing Director • Ophthalmology - Devices, Drugs, Diagnostics • E-mail: Darius Kharabi - [email protected] • Investment Size: $250k - $5M • Ophthalmology+ - Device, Drugs, Healthcare IT • Seed through human POC • Investment Size: $1M - $4M • www.forsightlabs.com • Seed to Early Stage • www.lagunitabio.com
• Jeffry Weinhuff - Managing Partner • E-mail: [email protected] • Ophthalmology - Devices, Drugs, Diagnostics • Investment Size: $1 - $5M • Michael Nissen, Firas Rahhal, Randolph Cohen, • Mid-Stage and Later • Ron Weiss, Robert Rothman, Jeffrey Smith - Managing Partners Alan Spiro, Adam Benowitz, James Murray, • www.visionaryvc.com • E-mail: [email protected] Maneesha Ghiya - Partners • Affiliated with 42 KOL’s and Launchpad SBDC • Ophthalmology - Devices, Drugs, Diagnostics • E-mail: [email protected] • Investment Size: $1 - $5M • Ophthalmology - Devices, Drugs, Diagnostics • Early to Late Stage • Investment Size: $250 - $500K • www.infocuscapitalpartners.com/ • Seed to Early Stage • www.exsightventures.com Piper Jaffray Senior Team Biographies: Udit Patel
Udit Patel is an executive director in the Piper Jaffray healthcare investment banking group, covering life sciences with a focus on ophthalmology. He is based in the firm’s San Francisco office. Prior to joining Piper Jaffray in 2013, Udit was vice president at UBS Investment Bank in New York, where his responsibilities included mergers and acquisitions as well as general advisory focused on healthcare. During his time at UBS, he successfully represented clients in a wide range of M&A transactions, with an aggregate transaction value exceeding $20 billion. Udit has 12 years of healthcare transaction experience, having successfully executed numerous M&A, equity, debt and equity-linked engagements. Before beginning his investment banking career, Udit was a consultant at Deloitte. Udit graduated with a bachelor’s degree in computer science from Cornell University. He earned a Master of Business Administration degree from the MIT Sloan School of Management.
Representative Transactions Mergers & Acquisitions IPOs Udit Patel $385,000,000 Undisclosed $605,000,000 $130,000,000 $175,000,000 $85,005,000 $138,000,000 Executive Director Acquisition of Acquired by Acquired by Acquired by Healthcare Investment Banking
+1 (415) 616-1855 Sole Financial Advisor Sole Financial Advisor Sole Financial Advisor Sole Financial Advisor Joint Bookrunner Joint Bookrunner Joint Bookrunner [email protected] $389,000,000 $277,000,000 $3,000,000,000 $96,000,000 $184,000,000 $64,400,000 $110,400,000
Acquisition of Acquisition of Acquired by Acquired by
Sole Financial Advisor Sole Financial Advisor Joint Financial Advisor Sole Financial Advisor Joint Bookrunner Joint Bookrunner Joint Bookrunner Includes deals completed at predecessor firms Drug and Device Ophthalmology M&A Deals Since October 2018
Announced Target Acquirer Enterprise Value ($M) 8/26/2019 Optotek Medical Quantel Medical ND 8/7/2019 Avedro Glaukos $500 7/24/2019 Moria Natixis / Naxicap Partners $46 7/15/2019 Hydrogel Vision Clerio Vision ND 6/25/2019 Allergan Plc AbbVie, Inc. $84,022 6/7/2019 Pleines Fashion Optik Brillen Rottler ND 5/9/2019 Luneau Technology Caravelle $157 5/8/2019 Xiidra (Shire) Novartis $5,300 4/8/2019 Ocugen, Inc. Histogenics ND 3/18/2019 Powervision Alcon $285 3/13/2019 D.O.R.C. International Eurazeo Capital $485 3/4/2019 Nightstar Therapeutics Biogen $800 2/25/2019 Spark Therapeutics Roche $4,800 2/19/2019 Linsenmax Kochoptik ND 2/19/2019 EM-100 (Eton Pharma) Bausch Health ND 2/18/2019 Innovalens Johnson & Johnson ND 1/30/2019 Helio Vision Aldeyra Therapeutics $25 1/8/2019 Blanchard Contact Lens CooperVision ND 1/7/2019 Microlens Contactlens Technology Ophtecs ND 12/20/2018 PhysIOL Beaver-Vistec ND 12/19/2018 Tear Film Innovations Alcon ND 10/31/2018 Inception 4 Ophthotech $12 10/23/2018 IanTECH Carl Zeiss Meditec ND 10/18/2018 MID Labs HOYA Surgical Optics $170
Courtesy of Udit Patel, Piper Jaffray Ophthalmology Licensing Deals Since October 2018 Date Upfront Deal Announced Licensor Licensee Lead Product Indication Payment ($M) Value ($M) 9/20/2019 Inflammasome BI Various Retinal Diseases ND $160 9/4/2019 Clearside Biomedical Regenxbio SCS Microinjector™ platform Suprachoroidal space delivery ND $136 8/23/2019 Iconic Novartis ICON-4 (anti-Tissue Factor) AMD ND ND 7/22/2019 Intratus Glaukos Various DED, glaucoma and other corneal diseases ND ND 7/10/2019 Clover Health Genentech (Roche) Development of personalized medicines Ocular diseases ND ND 7/1/2019 Odylia PTC RP-GRIP1 Rare Inherited Retinal Diseases ND ND 6/26/2019 Oxford BioMedica Santen Various gene therapy products Inherited Retinal Diseases ND ND 5/23/2019 Santhera Chiesi Farmaceutici Raxone® LHON $48 $102 4/26/2019 Santen Glaukos MicroShunt (DE-128) primary open-angle glaucoma (POAG) ND ND 4/8/2019 Alnylam Regeneron RNAi Therapeutics Ocular and CNS Diseases $800 $1,000 2/10/2019 Samsung Bioepis AffaMed LUCENTIS® wAMD ND ND 1/31/2019 MeiraGTx Janssen Various Inherited Retinal Diseases $100 $440 1/4/2019 Novartis Oculis LME636 (renamed OCS-02) Topical Anti-TNF Alpha Antibody ND ND 12/4/2018 ABL Bio TRIGR TR009 angiogenic factors (VEGF and DLL4) $5 $590 12/17/2018 Alvotech Fuji Pharma Ophtho Biosimilars Various NA $50 11/6/2018 U of Penn & Florida Ophthotech AAV gene therapy products Best vitelliform macular dystrophy ND ND 11/5/2018 EyePoint Ocumension Durasert™ Posterior Segment Uveitis $2 $12 10/29/2018 Ionis ProQR IONIS-RHO-2.5Rx (now QR-1123) adRP $3 ND 10/10/2018 Ionis Roche IONIS-FB-L Rx Complement-Mediated Diseases $75 $759 10/2/2018 OcuNexus Eyevance NEXAGON Persistent Corneal Epithelial Defect ND ND
Courtesy of Udit Patel, Piper Jaffray Barclays Team
David Parrot Will Han Brandon Kun Managing Director Associate Analyst [email protected] [email protected] [email protected] 650-289-6046 650-289-6147 650-289-6003
1 Ophthalmology M&A and Licensing Activity Ophthalmology Therapeutic M&A Activity
($ in millions) Therapeutics
(1) Date Target Acquiror Upfront Milestone Total Disease Area
6/25/2019 Allergan AbbVie $63,000 - $63,000 General Ophthalmology
5/8/2019 Xiidra from Shire / Takeda Novartis 3,400 1,900 5,300 Dry Eye
3/4/2019 Nightstar Biogen 800 - 800 Choroideremia, X-Linked Retinitis Pigmentosa
Fibrodysplasia Ossificans Progressiva, Multiple 2/25/2019 Clementia Ipsen 1,000 263 1,263 Osteochondromas, Dry Eye
2/22/2019 Spark Roche 4,800 - 4,800 Retinal Dystrophy, Choroideremia, Stargardt Disease
1/24/2019 Helio Vision Aldeyra Therapeutics 10 15 25 Proliferative Vitreoretinopathy
10/30/2018 Inception 4 IVERIC 6 - 6 HtrA1 inhibitor for retinal diseases
______Source: Company information, CapIQ, Cortellis. 1. Total includes upfront and potential milestone payments.
2 Ophthalmology Devices M&A Activity
($ in millions) Devices
(1) Date Target Acquiror Upfront Milestone Total Description Precision vascular robotic-assisted systems for use in 8/8/2019 Corindus Vascular Robotics Siemens Medical Solutions $1,118 - $1,118 interventional procedures Products to treat ophthalmic disorders and conditions, 8/7/2019 Avedro Glaukos 591 - 591 primarily associated with corneal weakness Sustained-relsease drug delivery platforms for retinal 6/19/2019 Dose Medical Glaukos 3 - 3 diseases Diagnostic systems for the early detection of sight- 4/13/2019 CenterVue Revenio 59 1 60 threatening pathologies
4/11/2019 Orbit Biomedical Gyroscope 38 - 38 Surgical devices in the subretinal space
Instruments and equipment for anterior and posterior 3/13/2019 Dutch Ophthalmic Research Center Eurazeo 486 - 486 ophthalmic surgery Products for the treatment of evaporative dry eye and 12/19/2018 Tear Film Innovations Alcon 145 - 145 related syndromes
10/18/2018 Medical Instrument Development Labs HOYA Medical 174 - 174 Develops and supplies ophthalmic products
______Source: Company information, CapIQ, Cortellis. 1. Total includes upfront and potential milestone payments.
3 Ophthalmology Licensing Activity
($ in millions) Date Licensor Licensee Upfront Milestone Total(1) Description 9/20/2019 Inflammasome Boehringer Ingelheim Undisc. Undisc. $160 Inflammasome and BI to develop up to three therapies using intravitreal drug delivery for retinal diseases 9/4/2019 Copernicus Wize Pharma Wize Pharma to use Copernicus's gene therapy technology for development of its WP-REP1 for choroideremia 8/22/2019 Iconic Therapeutics Novartis Novartis to develop Iconic's ICON-4 for age-related macular degeneration with an option 8/13/2019 Novartis Pharming Group 20 - 20 Pharming to develop and commercialize Novartis’ CDZ-173 for the treatment APDS in US, Europe and WW 7/29/2019 Medicom Aequus Aequus to distribute Medicom’s Evolve line of dry eye products in Canada 7/25/2019 Novartis Mundipharma Mundipharma to commercialize Novartis' medicines for eye diseases in Philippines, Thailand and Taiwan 7/22/2019 Intratus Glaukos Glaukos to develop Intratus’ drug delivery platform for dry eye disease, glaucoma and other corneal disorders 7/10/2019 Clover Genentech Clover Therapeutics and Genentech to conduct research on genetics of ocular diseases 7/1/2019 Guangdong Zhongsheng WuXi PharmaTech Wuxi PharmaTech to develop Guangdongl's ZSYM-011 for the treatment of diabetic macular edema 6/27/2019 Sun Pharmaceutical China Medical System CMS to develop and commercialize Sun Pharma's Cyclosporine A and Tildrakizumab for dry eye disease 6/26/2019 Oxford BioMedica Santen OXB and Santen to develop gene therapy products for inherited retinal disease with OXB's lentiviral vectors 6/25/2019 Novartis Premark Pharma Premark Pharma to develop and commercialize Novartis' PMP-2207 for blepharitis 6/12/2019 Allele Alpine Bio Allele and Alpine to develop human iPSC-derived cell therapy products against retinal diseases 6/3/2019 FUJIFILM Outlook FDB to manufacture and supply Outlook Therapeutics' ONS-5010 for the treatment of wet AMD 5/23/2019 Santhera Chiesi 50 55 105 Chiesi to develop Santhera's Raxone for LHON and other indications worldwide except the US and Canada 5/1/2019 AP Biosciences Allgenesis Allgenesis to develop AP Biosciences' AG-67650 for wet AMD 4/30/2019 SIFI Societa Zydus-Cadila Zydus Cadila to market SIFI's intraocular lenses and surgical products for ocular disorders in India 4/29/2019 Altus Formulation Tetra Bio-Pharma Tetra and Altus to form JV to develop cannabinoid receptor for pain, oncology and ophthalmology 4/28/2019 Yuyu Iris Pharma Yuyu and Iris to develop YDE-011 for the treatment of dry eye 4/26/2019 Glaukos Santen Glaukos to distribute Santen's MicroShunt for open angle glaucoma in the US 4/9/2019 ReNeuron Shanghai Fosun 8 105 113 Fosun Pharma to develop CTX and hRPC cell therapy programs against retinitis pigmentosa 4/8/2019 Alnylam Regeneron 800 200 1,000 Regeneron and Alnylam to develop RNAi therapeutics for ocular and CNS diseases worldwide 3/27/2019 MedPharm Destiny Pharma MedPharm to provide development services to Destiny for XF-platform compounds against ocular infections 3/25/2019 Pharmaceuticals International Emerald Bioscience Pii to provide development services to Emerald's NB-1111 3/18/2019 OliX Pharmaceuticals Inc Laboratoires Thea 2 - 2 Thea to develop and commercialize OliX's OLX-301A against AMD in EU, Middle East and Africa 3/14/2019 Santen Hanmi Hanmi to jointly distribute Santen's Diquas and Diquas-S for dry eye treatments in South Korea
______Source: Company information, Cortellis. 1. Total includes upfront and potential milestone payments.
4 Ophthalmology Licensing Activity (cont’d)
($ in millions) Date Licensor Licensee Upfront Milestone Total(1) Description 2/25/2019 Noramco Emerald Bioscience $0.3 - $0.3 Noramco to manufacture Emerald's analog of cannabidiol 2/18/2019 Eton Pharmaceuticals Bausch & Lomb 1 3 3 Bausch & Lomb acquires Eton's EM-100 for ocular itching associated with allergic conjunctivitis in the US 2/10/2019 Samsung Bioepis AffaMed Samsung Bioepis and AffaMed to develop biosimilars including SB-11, SB-12 and SB-3 in China 1/30/2019 MeiraGTx Janssen 100 340 440 Janssen to develop and commercialize MeiraGTx's gene therapies against inherited retinal diseases WW 1/18/2019 Covance OliX Pharmaceuticals Covance to provide OliX with GLP toxicology study services for OLX-10020 in GA and OLX-101 in scarring 1/16/2019 Protheragen Everglades Bio Protheragen and Everglades to develop anti-Scg3 antibody for DR, PDR and other diseases 1/7/2019 Orbit Biomedical Lineage Cell BioTime to evaluate Orbit Biomedical's injection technology to deliver OpRegen for the treatment of dry-AMD 12/21/2018 Novaliq NicOx SA Nicox and Novaliq to develop topical ophthalmic formulations of NO-donating PDE5 inhibitors 12/11/2018 Rhodes Technologies Tetra Bio-Pharma Rhodes Technologies to supply THC to Tetra Bio-Pharma for development of PPP-002, PPP-003, and PPP-004 12/3/2018 ABL Bio TRIGR Therapeutics 5 590 595 TRIGR to develop and commercilaize ABL Bio's ABL-001 for oncology and ophthalmology indications 11/30/2018 Glauconix Biosciences Emerald Bioscience Glauconix to conduct research for Nemus Bioscience's NB-1111 using 3D HTM model against glaucoma 11/30/2018 Santen Pharmaceutical Meiji Seika Pharma Meiji Seika to distribute Santen’s Diquas and Taflotan in Indonesia for ocular conditions 11/20/2018 Quantum Pharma Tetra Bio-Pharma Quantum to produce cannabis and cannabinoid drug products for Tetra Bio-Pharma 11/13/2018 ORA ProQR Therapeutics Ora to provide Ora's VNC mobility services to ProQR to develop QR-110 in LCA Type 10 11/5/2018 Beta Therapeutics Oxurion Oxurion received an option for developing heparanase inhibitors for retinal disorders, including dry AMD 10/29/2018 Ionis Pharmaceuticals ProQR Therapeutics Undisc. Undisc. 3 ProQR to develop Ionis' QR-1123 for adRP 10/24/2018 Amgen Orion Orion to commercialize Amgen's Amgevita for chronic inflammatory diseases in Finland 10/24/2018 MacuLogix Optos Optos to market MacuLogix's AdaptDx for dry AMD in Europe and Australia 10/23/2018 Clarion Medical MacuLogix Clarion to distribute MacuLogix's AdaptDx automated dark adaptometer to diagnose AMD, in Canada 10/9/2018 Ionis Pharmaceuticals Roche 75 684 759 Roche to develop Ionis's IONIS-FB-LRx for Geographic Atrophy worldwide, with an option to commercialize 10/2/2018 Ocunexus Therapeutics Eyevance Eyevance to develop and commercialize OcuNexus' Nexagon for persistent corneal epithelial defect WW 9/28/2018 Melinta Therapeutics The Menarini Undisc. Undisc. 269 Menarini to codevelop Vabomere, Orbactiv and Minocin in Europe, Asia-Pacific, Korea, Australia and CIS 9/26/2018 Sonoma Pharmaceuticals Brill Pharma Brill to develop Sonoma's antimicrobial hypochlorous acid eye solution for blepharitis 9/25/2018 PeptiDream Santen Santen and PeptiDream to discover macrocyclic/constrained peptides against ophthalmic disease 9/19/2018 Novartis IDEAYA 3 29 32 Ideaya to develop and commercialize Novartis' LXS-196 against MUM worldwide
______Source: Company information, Cortellis. 1. Total includes upfront and potential milestone payments.
5 Ophthalmology Opportunity Roadmap Ophthalmic Opportunity Roadmap
Glaucoma Dry Eye AMD Other
/ (Lacrisert) / (Multiple) (Xiidra) / (Macugen, (Durasert, Marketed (Rhopressa & (DE-117, (Diquas, Hyalein, (BromSite – (Jetrea –(Dextenza for (Iluvien – Visudyne) Rocklatan) (Vyzulta) DE-128) (Seciera) Ikervis) (Eylea – Wet AMD, DME) (Multiple) (Luxturna – IRD)Cataract surgery) Dexycu) VMA) Post-Op Pain) (Multiple) DME) / (MIM-D3) (Reproxalap –allergic (NSR-REP1 for (Beovu – Wet AMD [Filed]) (DE-109 – Uveitis (NDA Filed)) (CLS-1001 – Uveitis [Filed]) conjunctivitis) choroidemia) (CyclASol) (KPI-121) / (SkQ1) (SHP640 – Phase III (Renexus - Macular (OTX-DP for (Abicipar – Wet AMD & DME [Filed]) Infectious Conjunctivitis) (Stargardt Disease) (ADV-2191 – (OTX-TP) (TOP1630) Telangiectasia) Allergic Conjunctivitis) (RGN-259) proliferative vitreoretinopathy) (Faricimab – Wet AMD) (QLT091001 – (APL-2 – GA) (Ranibizumab + Port (GS010 – Gene LCA and RP) (OC-01) (Reproxalap) Delivery System – DME) (Elamipretide – LHON) therapy for LHON)
/ / / (X-82 oral anti-VEGF + (ASP7317 Cell / / (GS030 – Gene / anti-PDGF – Wet AMD) (OPT-302 – Wet AMD) therapy for RP) (Multiple) (OXB-202 – Corneal Graft Rejection) (ENV515) (Helios insert) Therapy – Dry AMD) (Luminate – DME) (TAK-759) / (KDV001 / / (UNR844 – Presbyopia) – DME) / / (HORA-RPE65 (ASP7317 – Stargardt Disease) / (Luminate – Wet AMD) (ICON-1 – Wet AMD) Presbyopia – RPE65) (DE-126) (ECF843) Therapies (L-PDDS) / (Liquid Vision / Phase II (Gene therapy for XLRS, ACHM, XLRP) – Presbyopia) (Zimura – GA) (SAR 422459/421869 – (Pan-90806 topical – Stargardt / Usher) (Optiquel – Wet AMD) Autoimmune uveitis) (OCS-02) (Zimura – (PP-001 – Uveitis, (Renexus) (VS-101) (OC-02) (GB-102 – Wet AMD) (RGX-314 – Stargardt disease) Conjunctivitis) (OpRegen – Dry AMD) Wet AMD) (CLS-1001 – DME) (MI-100 – Stargardt disease) / (LKA651 – DME) / (Voclosporin Ophthalmic (Elamipretide – (OCS-01 – DME; OCS- (ALK-001 – (ReN003 – hPRC (AAV-CNGB3 (ANX007 – P1/2) (IONIS-FB-LRX – Dry AMD) Solutions) Dry AMD) 02 – Uveitis ) Stargardt disease) Therapy for RP) AAV-RPE65, AAV-RPGR)
/ /(AGN-151597 – Gene (ADVM-022 – (KSI 301 – Diabetic (ONL1204 for Phase I (OXB-201 – (KSI 301 – Wet / Therapy for RP) Wet AMD) (HMR59) AMD) Wet AMD) Retinopathy) (EBI-031– Macular oedema) (EDIT-101 - LCA) retinal detachment)
(VP1-001 – Cataracts, Presbyopia) (4D-110 – (Usher) (TMi-018 – Geographic Atrophy) (RP) (Multiple gene therapy Choroideremia) Pre-Clinical (GB-201, (SURF-100, GB-202, (RPE-P – (ONL1204 – programs for retinal diseases) SURF-200, SURF- (JDE-001) (KSI 401 – Dry GB-203) Dry AMD) Wet & Dry AMD) (KSI 501 – DME 300) AMD) (VM200 – Stargardt, (PRO-001 for RP) & Uveitis) Sjogren) (Multiple ophth diseases) ______Source: Company information. DR = Diabetic Retinopathy, RVO = Retinal Vein Occlusion, XLRS = X-Linked Retinoschisis.
6 Ophthalmic Opportunity Roadmap (cont’d)
Glaucoma / IOP
(Rhopressa & / Marketed Rocklatan) (Vyzulta) (DE-117, DE-128)
Phase III (OTX-TP)
/ (ENV515) (Helios insert) (DE-126)
Phase II (Renexus)
(VS-101) (L-PDDS) (ANX007 – P1/2)
Phase I
Pre-Clinical (GB-201, GB-202, GB-203)
______Source: Company information.
7 Ophthalmic Opportunity Roadmap (cont’d)
Dry Eye
Marketed (Seciera) (Xiidra) (Diquas, Hyalein, Ikervis) (Lacrisert)
(RGN-259) / (CyclASol) Phase III (Reproxalap) (TOP1630) (MIM-D3) (OC-01) (KPI-121) (SkQ1)
/ / (TAK-759) (ECF843)
Phase II
(Voclosporin (OCS-02) (OC-02) Ophthalmic Solutions)
Phase I
Pre-Clinical (SURF-100, SURF-200, (JDE-001) SURF-300)
______Source: Company information.
8 Ophthalmic Opportunity Roadmap (cont’d)
Wet AMD Dry AMD
Marketed / / (Macugen, (Eylea) Visudyne)
/ Phase III (Beovu) (Abicipar) (APL-2 – GA) (Faricimab)
/ (X-82 oral anti-VEGF + anti-PDGF) (GB-102) (ICON-1) / (IONIS-FB-LRX) (ASP7317 Cell Therapy)
Phase II / / (OPT-302) (Luminate) (Zimura – GA)
(OpRegen) (Pan-90806 topical) (RGX-314) (Elamipretide)
Phase I (ADVM-022 gene (HMR59) (KSI 301) (OXB-201) therapy)
Pre-Clinical (ONL1204) (TMi-018 – GA) (ONL1204) (RPE-P) ______Source: Company information.
9 Ophthalmic Opportunity Roadmap (cont’d)
Gene Therapy / Editing Cell-Based Therapy
Marketed (Luxturna – Inherited retinal dystrophies)
Phase III (NSR-REP1 for (GS010 – LHON) choroidemia)
/ / (Stargardt disease, Usher (ASP7317 – Dry AMD, (Renexus - Macular Syndrome type 1B) Stargardt Disease) Telangiectasia and Glaucoma) / (Zimura - Phase II (XLRS, ACHM, XLRP) Stargardt Disease) (AAV-CNGB3 AAV-RPE65, AAV-RPGR) (ReN003 – hPRC Therapy (HORA-RPE65 – RPE65) (OpRegen – Dry AMD) (RGX-314 – Wet AMD) for RP) / / Phase I (OXB-201 – (ADVM-022 – Wet AMD) (AGN-151597 – RP) (HMR59 – Dry AMD)(EDIT-101 - LCA) Wet AMD)
(Multiple gene therapy Pre-Clinical (RP) (Usher) (4D-110 – programs for retinal Choroideremia) diseases)
______Source: Company information. LCA = Leber Congenital Amaurosis, LHON = Leber’s Hereditary Optic Neuropathy, XLRS = X-Linked Retinoschisis.
10 Ophthalmic Opportunity Roadmap (cont’d)
Sustained Release Neuroprotection
(Durasert – Marketed (Iluvien - DME) (Dexycu – Post- (Dextenza for Uveitis) ocular surgery) Post-Op Pain)
Phase III (OTX-DP for (Renexus - Macular (Beovu – Wet AMD) (Ranibizumab + Port (Renexus - Macular Allergic Conjunctivitis) Telangiectasia) Delivery System – DME) Telangiectasia)
/ / (Luminate – Wet AMD, (L-PDDS – Glaucoma) DME) Phase II
(VS-101 Insert - Glaucoma) (KDV001 – DME) (ANX007 – Glaucoma – P1/2)
Phase I
Pre-Clinical (PRO-001 for (PRO-001 – RP) RP)
______Source: Company information.
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12 OPHTHALMOLOGY MARKET OVERVIEW
October 2019
HEALTHCARE INVESTMENT BANKING RAYMOND JAMES TEAM
Andrew Gitkin Kyle Madan Managing Director and Director Co-Head Healthcare Investment Banking Healthcare Investment Banking [email protected] [email protected]
93 TABLE OF CONTENTS
SECTION 1 Macro View and Financing Trends
SECTION 2 Ophthalmology Roadmap
SECTION 3 Ophthalmology M&A and Licensing
SECTION 4 Key Clinical Events
SECTION 5 Upcoming Catalysts and Ongoing Trials
94 MACRO VIEW AND FINANCING TRENDS
Section 1
95 OPHTHALMOLOGY ROADMAP
Section 2
96 OPHTHALMIC OPPORTUNITY ROADMAP
Glaucoma Dry Eye AMD Other
Marketed
Phase III
Phase II
Phase I
EyGen
Pre-Clinical
Note: Includes select ophthalmology companies by clinical status, target indication, and phase of development as of 09/30/2019 97 Source: Company filings, Company website, and ClinicalTrials.gov OPHTHALMIC OPPORTUNITY ROADMAP (CONT’D)
Glaucoma / IOP
Marketed (Rocklatan; (Alphagan; Combigan; (CyPass) (Istalol; Vyzulta) (iStent inject) (Azopt; Simbrinza) (Rescula) (Xelrpros) Rhopressa) XEN Gel)
Phase III
(Bimatoprost SR) (OTX-TP) (DE-111A; DE-117; DE-128)
Phase II (Evolute) (Renexus) (ENV515) (PHP-201) (DE-126) (Bamosiran)
Phase I (OTX-TIC) (ECP-105) (ANX007)
Pre-Clinical (TODDD) (GB-201, GB-202, GB-203)
Note: Includes select ophthalmology companies by clinical status, target indication, and phase of development as of 09/30/2019 98 Source: Company filings, Company website, and ClinicalTrials.gov OPHTHALMIC OPPORTUNITY ROADMAP (CONT’D)
Dry Eye
Marketed (Diquas, Hyalein, (Restasis) (Xiidra) (Cequa) (Softacort) (Klarity-C) Ikervis)
(OCU-310) (OC-01, OC-02) (MIM-D3) (RGN-259) (Reproxalap) (MC2-03 PAD) (Visomitin) (EGP-437) Phase III (EBI-005) (CyclASol, (KPI-121) NOV03) (RGN-259) (SJP-0035) (Rebamipide) (SYL1001) (AGN-195263)
(Cis-UCA) (SDP-4) (TOP1630) (ECF843) (CP-690,550) (Voclosporin) Phase II (P-321) (Pro-Ocular) (AVX-012)
(AL-43546) (OCS-02) (Ecabet) (Lacriprep) (Elate Ocular) (RP101) (rhNGF) (DE-101)
Phase I (Palovarotene) (PaniDrop) (OCU-001) (IC265)
EyGen Pre-Clinical (OTX-CSI) (ALY688) (PPL-003) (KPI-190) (SURF-100) (OKYO-0101) (NaV 1.7) (Joint Venture)
Note: Includes select ophthalmology companies by clinical status, target indication, and phase of development as of 09/30/2019 99 Source: Company filings, Company website, and ClinicalTrials.gov OPHTHALMIC OPPORTUNITY ROADMAP (CONT’D)
Wet AMD Dry AMD
(Lucentis) Marketed (Eylea) (Macugen) (Visudyne)
Phase III (Ranibizumab PDS; (APL-2 – GA) (RTH258) (Abicipar) Faricimab)
(OPT 302) (AKST4290) (DE-122) (GB-102) (Zimura – GA) (IONIS-FB-LRx) (OpRegen – Dry AMD) (OpRegen)
(RG7716) (RGX-314) Phase II (PAN-90806) (PF582) (ICON-1) (Tesidolumab – GA) (CNTO 2476) (Elamipretide) (LHA510) (SFO166) (Luminate – Wet (KSI-301) AMD, DME) (ASP7317) (Xiflam – GA)
Phase I OTX-TKI – (Retinostat) (ADVM-022/032) (GT005) (NGM621) Wet AMD
(ONL1204) (AR-13154) (OCU200) Pre-Clinical (TMi-018) (ONL1204) (OLX301A) (BB-201) (OLX301A)
Note: Includes select ophthalmology companies by clinical status, target indication, and phase of development as of 09/30/2019 100 Source: Company filings, Company website, and ClinicalTrials.gov OPHTHALMIC OPPORTUNITY ROADMAP (CONT’D)
Gene Therapy Cell-Based Therapy
Marketed (Luxturna – Inherited retinal dystrophies)
Phase III (NSR-REP1 – (Renexus - Macular (GS-010 – LHON) (SPK-7001 – Choroideremia) Choroideremia) Telangiectasia)
(XLRP – Pigmentosa ACHM – (OXB-202 – Corneal Graft Achromatopsi; (RGX-314 – Wet AMD) Rejection; SAR-422549 – (ASP-7317 – Dry AMD; (Renexus - Glaucoma) XLRS – X-Linked Retinoschisis) Stargardt Disease; SAR- Stargardt Disease) Phase II 421869 – Usher Syndrome)
(ReN003 – hPRC (OpRegen – Dry AMD) (QR-110 – LCA) (GS-010 – RP) (NSR-RPGR – XLRP) Therapy for RP)
Phase I (ADVM-022 – (OXB-201 – Wet AMD) Wet AMD)
RGX-314 – (ADVM-022 Leber Congenital Pre-Clinical (Bionic Sight – Diabetic (OXB-204/208 – (Stargardt – Diabetic Amaurosis; Usher Optogenetics) Retinopathy; Anti- Ophthalmology) Retinopathy) Diease) Syndrome VEGF
Note: Includes select ophthalmology companies by clinical status, target indication, and phase of development as of 09/30/2019 101 Source: Company filings, Company website, and ClinicalTrials.gov OPHTHALMIC OPPORTUNITY ROADMAP (CONT’D)
Sustained Release Neuroprotection
Marketed (Iluvien - DME) (Yutiq – Uveitis; Dexycu – (Dextenza – Post-Op (Retisert – Uveitis) (Ozurdex – DME, Post-Ocular Surgery) Pain and Inflammation) BRVO, and uveitis)
Phase III (Anti VEGF (Dextenza - Allergic (Ranibizumab + (Bimatoprost SR – (Renexus - Macular (Renexus - Macular RTH258 – Wet Conjunctivitis; OTX-TP - Port Delivery Glaucoma and Telangiectasia) Telangiectasia) AMD (NDA filed)) Glaucoma and Ocular System – DME) Ocular Hypertension Hypertension) (NDA filed))
Phase II (KDV001 – DME) (Luminate – WetAMD, DME) (Evolute – Glaucoma) (Renexus - Glaucoma)
(TLC399 – Macular Edema) (Renexus - Glaucoma)
Phase I (OTX-TIC – Glaucoma and Ocular Hypertension; OTX-TKI – Wet AMD, (AR-13503 implant – DME, and RVO) Neovascular AMD, DME) (ANX007 – Glaucoma)
(OTX-CSI – Dry Eye; OTX-KTO – Allergic Pre-Clinical (OTX-IVT) – Wet AMD, Conjunctivitis; OTX-BDI – Post-Op Pain and (TODDD – Glaucoma) DME, and RVO Inflammation; OTX-BPI – Acute Ocular Pain)
Note: Includes select ophthalmology companies by clinical status, target indication, and phase of development as of 09/30/2019 102 Source: Company filings, Company website, and ClinicalTrials.gov OPHTHALMOLOGY M&A AND LICENSING
Section 3
103 OPHTHALMOLOGY M&A ACTIVITY
Upfront Transaction Date Target Acquirer Payment ($M) Value ($M) Description 09/04/19 Ophthalmic Instruments Advancing Eyecare NA NA Distributes ophthalmic equipment and supplies 08/14/19 Fokus Optik Middlecap Partners NA NA Offers spectacle frames, contact lenses, and optometric services 08/02/19 Spex Opticians Bayfield & Bartlam Optical NA NA Spectacle maker and eye care center 07/24/19 Moria Natixis Private Equity $43.0 $43.0 Develops and manufactures instruments for ophthalmic surgery 07/15/19 Hydrogel Vision Clerio Vision NA NA Manufactures contact lens 06/24/19 ARGES Novanta, Inc. NA NA Manufactures laser scan systems for ophthalmology applications 06/20/19 Look Optics SEOULEAGUER $14.2 $14.2 Offers sunglasses and eyeglass lenses and frames 05/24/19 Wöhlk Contactlinsen Seed $1.8 $1.8 Manufactures contact lenses 05/09/19 Takeda (Xiidra) Novartis $3,400.0 $5,300.0 Assets related to Xiidra, a drug for dry eye disease 04/04/19 Sucampo (Rescula Eye Drops) Nitto Medic Co., Ltd. NA NA Manufactures medical eye drops 03/29/19 Brillenbär Verwaltungs GrandVision Europe NA NA Supplies optical goods 03/13/19 D.O.R.C. Eurazeo Capital $484.8 $484.8 Manufactures ophthalmic surgical disposables, instruments, and units 03/04/19 Nightstar Therapeutics Biogen $877.4 $877.4 Clinical-stage gene therapy company 02/25/19 Spark Therapeutics Roche $4,851.2 $4,851.2 Develops gene therapies to treat inherited retinal sickness 02/19/19 Linsenmax Kochoptik AG NA NA Manufactures contact lenses and eye care and optical products 02/11/19 Metalizado Optico Argentino EssilorLuxottica SA NA NA Manufactures prescription lenses 01/07/19 Microlens Contactlens Technolgy Ophtecs NA NA Manufactures contact lens 12/19/18 Tear Film Innovations Alcon NA NA Products for the treatment of evaporative dry eye and related syndromes 12/06/18 Hemics Demcon Mechatronics NA NA Manufactures optical inflammation detection technology 11/30/18 Eye Care & Cure Blue Point; The Hilsinger NA NA Ophthalmic and optometric surgical supplies, diagnostics, and instruments 10/31/18 Inception 4 IVERIC bio (Ophthotech) NA NA Develops drugs to treat retinal eye disease 10/28/18 Medone Surgical D.O.R.C. NA NA Manufactures ophthalmic cannulae, backflush instruments, and more
Note: Includes healthcare M&A deals within or related to ophthalmology within the last twelve months 104 Source: Company filings, CapIQ market data as of 9/30/2019 OPHTHALMOLOGY LICENSING ACTIVITY
Upfront Total Date Licensor Licensee Drug Name Indication Phase Description Value ($M) Value ($M) 09/16/19 AdAlta GE Healthcare I-Body Wet AMD Phase 2 AdAlta secures licensing deal for the i-body platform NA NA 09/09/19 Copernicus Wize Pharma WP-REP1 Choroideremia Pre-clinical Wize Pharma enters exclusive license agreement NA NA 09/04/19 Clearside REGENXBIO RGX-314 Wet AMD Pre-clinical REGENXBIO announces worldwide option/ license agreement NA NA 08/22/19 Iconic Novartis ICON-4 Wet AMD Pre-clinical Iconic signs option agreement for ICON-4 NA NA 07/23/19 UMass IVERIC bio LCA10 Minigene Leber's amaurosis Approved UMass Medical School licenses gene therapy to IVERIC bio NA NA 07/02/19 Nicox Ocumension NCX 4251 Ocular pain Pre-clinical Nicox signs agreement for NCX 4251 in China €2.0 €12.0 06/27/19 Sun Pharma China Medical Cequa Dry eye Phase 2 Sun and China Medical enter into a license agreement NA NA 05/23/19 Santhera Chiesi Group Raxone Leber's neuropathy Pre-clinical Santhera enters into license agreement with Chiesi $50.0 $105.0 03/18/19 OliX Théa Open OLX-301 Wet AMD Phase 2 Théa and OliX announce collaboration to develop RNAi €2.0 NA 03/15/19 Nicox Ocumension ZERVIATE Allergic conjunctivitis Phase 2 Nicox/ Ocumension enter license agreement for ZERVIATE NA NA 02/11/19 Samsung AffaMed Ranibizumab Wet AMD Phase 3 Samsung and AffaMed to develop biosimilars in China NA NA 01/31/19 MeiraGTx Janssen AAV Achromatopsia Approved Janssen and MeiraGTx to develop gene therapies $100.0 $440.0 01/04/19 Novartis Oculis OCS-02 Dry eye Pre-clinical Oculis in-licenses anti-TNF alpha antibody fragment NA NA 01/03/19 Ascentage UNITY UBX1967 DME Phase 2 UNITY executes a license agreement for UBX1967 NA NA 12/17/18 Nicox Ocumension NCX 470 Glaucoma Approved Nicox and Ocumension to develop and NCX 470 in China €3.0 €36.3 11/05/18 Beta Oxurion Heparanase Dry AMD Pre-clinical Oxurion and Beta to develop new heparanase inhibitors NA NA 11/05/18 EyePoint Ocumension Iluvien Uveitis Phase 2 EyePoint and Ocumension to develop Durasert in China $1.8 $11.8 10/31/18 UPenn; UFRF IVERIC IC-200 Retinopathy Pre-clinical IVERIC obtains exclusive global license to AAV gene therapy NA NA 10/29/18 Ionis ProQR QR-1123 Retinitis pigmentosa Phase 2 ProQR in-licenses worldwide rights from Ionis $2.5 NA 10/24/18 Amgen Orion Amjevita Uveitis Pre-clinical Orion and Amgen to collaborate on AMGEVITA in Finland NA NA 10/02/18 OcuNexus Eyevance Nexagon Corneal epithelial defects Pre-clinical Eyevance acquires worldwide rights to NEXAGON NA NA
Note: Includes last twelve months healthcare licensing deals where the licensee company is in the ophthalmology industry sector 105 Source: Company filings, CapIQ market data as of 9/30/2019 KEY CLINICAL EVENTS
Section 4
106 RECENT KEY OPHTHALMOLOGY PHASE 2 ACTIVITY
Date Company Drug Name Indication Phase/ Trial Name Description 09/12/19 Adverum (1) ADVM-022 Wet AMD Phase I - OPTIC Phase 1 data from first cohort presented September 12, 2019. Range change in BCVA -9.1 to +5.1 letters 08/06/19 Opthea Limited OPT-302 Wet AMD Phase IIb - w/Lucentis Opthea meets primary endpoint in Phase II study of OPT-302 in Wet AMD
06/04/19 Allegro Ophthalmics Risuteganib Wet AMD Phase II - Intermediate Allegro announces positive topline vision results of Phase II study evaluating risuteganib 05/14/19 MeiraGTx AAV-RPE65 Wet AMD Phase I/II - OPTIRPE65 Meiragtx announces positive 6-month data from Phase I/II trial of investigational gene therapy 04/28/19 Stealth BioTherapeutics Elamipretide Wet AMD Phase I/II - ReCLAIM Stealth Biotherapeutics announces positive results for elamipretide in ophthalmic conditions 04/26/19 Akari Therapeutics Coversin Allergic Conjunctivitis Phase I/II - TRACKER Akari Therapeutics announces expanded ophthalmology program based on positive emerging data 01/22/19 Aurinia Voclosporin Dry Eye Phase IIa - vs. Restasis Aurinia announces Voclosporin ophthalmic solution demonstrates statistically superior efficacy versus restasis 01/21/19 GrayBug GB-102 Wet AMD Phase I/IIa - ADAGIO Graybug Vision presents top line results of Phase I/IIa adagio study
12/17/18 Alkahest AKST4290-201/ 202 Wet AMD Phase IIa - ALK4290-201 Alkahest announces positive top-line data from two Phase IIa studies
10/27/18 Roche Holding Faricimab Wet AMD Phase II - STAIRWAY New stairway study data shows potential for extended durability with Roche’s Faricimab 10/24/18 Oyster Point Pharma OC-02 Dry Eye Phase IIb - RAINIER Oyster Point announces positive results from two separate Phase IIb clinical trials 10/24/18 Oyster Point Pharma OC-01 Nasal Spray Dry Eye Phase IIb - ONSET-1 Oyster Point announces positive results from two separate Phase IIb clinical trials
Note: Includes selected key ophthalmology Phase 2 events within the last twelve months 107 Source: Company filings and Informa Market Research as of 9/30/2019 (1) Includes meaningful WET-AMD results from ADVM reported on 9/12/2019 RECENT KEY OPHTHALMOLOGY PHASE 3 ACTIVITY
Date Company Drug Name Indication Phase/Trial Name Description 08/07/19 TopiVert Pharma TOP1630 Dry Eye Phase IIb/III - THEIA-1 Topivert announces top-line results from Theia-1 Phase IIb/III clinical study of TOP1630 as a treatment for dry eye disease 06/25/19 Aldeyra Therapeutics Reproxalap Allergic Conjunctivitis Phase III - Seasonal Aldeyra Therapeutics reported that its reproxalap failed to meet its primary or secondary endpoints 05/20/19 Ocular Therapeutix OTX-TP Glaucoma Phase III - vs. Placebo Ocular Therapeutix announces topline results of Phase III clinical trial of OTX-TP for the treatment of glaucoma 05/06/19 Osmotica RVL-1201-202/ 203 Blepharoptosis Phase III - Acquired Blepharoptosis Osmotica Pharmaceuticals PLC announces positive topline results of Phase III clinical trials of RVL-1201for acquired blepharoptosis 05/05/19 Eyenovia MicroStat Mydriasis Phase III - MIST-1 Eyenovia announces presentation of successful Phase III studies from two Phase 3 MicroStat trials 04/02/19 Allergan Abicipar Pegol Wet AMD Phase III - MAPLE Allergan and Molecular Partners announce topline safety results from maple study of abicipar pegol 03/26/19 Aldeyra Therapeutics Reproxalap Allergic Conjunctivitis Phase III - ALLEVIATE Aldeyra announces positive top-line results from the Phase III alleviate trial in patients with allergic conjunctivitis 02/28/19 Horizon Pharma Teprotumumab Thyroid eye disease Phase III - OPTIC Horizon Pharma announces Phase 3 confirmatory trial evaluating teprotumumab (optic) for the treatment of active thyroid eye disease (TED) 02/25/19 Eyenovia MicroStat Mydriasis Phase III - MIST-2 Eyenovia announces confirmatory results from second microstat Phase III registration study for mydriasis 02/04/19 GenSight Biologics GS010 Leber's Neuropathy Phase III - RESCUE Gensight Biologics reports topline results at week 48 of the rescue Phase III clinical trial of GS010 01/31/19 Sylentis SYL1001 Dry Eye Phase III - HELIX Sylentis announces results of Phase III HELIX trial with tivanisiran for the treatment of dry eye disease 01/07/19 Allergan Bimatoprost Glaucoma Phase III - 092 Allergan announces positive 3-month topline results from second Phase III study of Bimatoprost
Note: Includes selected key ophthalmology Phase 3 events within the last twelve months 108 Source: Company filings and Informa Market Research as of 9/30/2019 RECENT OPHTHALMOLOGY APPROVALS
Date Company Drug Name Indication Event Type Description 09/20/19 Santen Alesion Allergic Conjunctivitis Regulatory - Supplemental Approval (Japan) Santen announces receipt of manufacturing and marketing approval of Alesion
09/03/19 Roche Holding Lucentis Retinopathy Regulatory - Supplemental Approval (Europe) European Commission approves Lucentis in infants with retinopathy of prematurity
08/05/19 Alimera Sciences Iluvien Diabetic Macular Edema Regulatory - Approval (Australia/New Zealand) Alimera announces Iluvien regulatory approval in Australia for the treatment of diabetic macular edema 03/25/19 Alimera Sciences Iluvien Uveitis Regulatory - Mutual Recognition Approval (Europe) Alimera Sciences announces approval received in the mutual recognition procedure for new indication for Iluvien in Europe 03/21/19 Alimera Sciences Iluvien Diabetic Macular Edema Regulatory - Approval (Emerging Markets) Alimera Sciences announces approval for Iluvien in Kuwait
03/12/19 Aerie Pharmaceuticals Rocklatan Glaucoma Regulatory - Approval (U.S.) Aerie Pharmaceuticals announces U.S. FDA approval of Rocklatan
03/11/19 Wize Pharma LO2A Dry Eye Regulatory - Approval (Europe) - Individual Country LO2A is granted market approval for the treatment of Sjögren's Syndrome in Hungary
02/25/19 Bausch Health Companies Lotemax SM Ocular Pain Regulatory - Approval (U.S.) Bausch + Lomb announces FDA approval of Lotemax (loteprednol etabonate ophthalmic gel)
02/20/19 AbbVie Humira Uveitis Regulatory - Approval (Canada) Abbvie's Humira approved by Health Canada to treat pediatric patients with chronic non- infectious anterior uveitis 02/05/19 Alimera Sciences Iluvien Diabetic Macular Edema Regulatory - Approval (Emerging Markets) Alimera Sciences announces approval for Iluvien in Lebanon
01/07/19 Santen Pharmaceutical Verkazia Allergic Conjunctivitis Regulatory - Approval (Canada) Santen annouced the approval of Verkazia in Canada
01/04/19 Bausch Health Companies Vyzulta Glaucoma Regulatory - Approval (Canada) Vyzultatm approved in Canada by Nicox’s partner
12/03/18 Ocular Therapeutix Dextenza Ocular Pain Regulatory - Approval (U.S.) Ocular Therapeutix announces FDA approval of DEXTENZA® for the treatment of ocular pain following ophthalmic surgery 11/23/18 Alimera Sciences Iluvien Diabetic Macular Edema Regulatory - Approval (Canada) Alimera Sciences announces Canadian regulatory approval for Iluvien
11/22/18 Spark Therapeutics Luxturna Leber's Amaurosis Regulatory - Approval (Europe) European Commission approves Spark Therapeutics’ Luxturna, a one-time gene therapy for inherited retinal disease
Note: Includes selected key ophthalmology related approval events within the last twelve months 109 Source: Company filings and Informa Market Research as of 9/30/2019 UPCOMING CATALYSTS AND ONGOING TRIALS
Section 5
110 SELECT UPCOMING DATA CATALYSTS
Timing (1) Company Symbol Drug Indication Catalyst Title Late 2019 Aerie Pharmaceuticals, Inc. AERI AR-1105 Macular Edema Phase II - Top-Line Results Late 2019 Annexon Biosciences Private ANX-007 Glaucoma Phase Ib - Top-Line Results Late 2019 Applied Genetic Technologies Corporation AGTC ACHM-B3 Congenital Blindness Phase I/II ACHM B3 - Top-Line Results Late 2019 Applied Genetic Technologies Corporation AGTC AGTC-402 Congenital Blindness Phase I/II - Top-Line Results Late 2019 Applied Genetic Technologies Corporation AGTC BIIB087 Congenital Blindness Phase I/II - Final Results Late 2019 Applied Genetic Technologies Corporation AGTC BIIB088 Retinitis Pigmentosa (RP) Phase I/II - Top-Line Results Late 2019 Biogen, Inc. BIIB BIIB112 Retinitis Pigmentosa (RP) Expansion Study - Top-Line Reults Late 2019 Bionure, Inc. Private BN201 Optic Neuritis Phase I - Top-Line Results Late 2019 GenSight Biologics S.A. SIGHT:FP GS-030 Retinitis Pigmentosa (RP) Phase I/II PIONEER - Top-Line Results Late 2019 Hovione LLC Private HY02 Ocular Pain and/or Inflammation Phase I - Top-Line Results Late 2019 Johnson & Johnson JNJ AAV-CNGB3 Congenital Blindness Phase I/II - Top-Line Results Late 2019 Johnson & Johnson JNJ AAV-RPGR Retinitis Pigmentosa (RP) Phase I/II - Top-Line Results Late 2019 Kala Pharmaceuticals, Inc. KALA KPI-121 0.25% Dry Eye Phase III STRIDE 3 - Top-Line Results Late 2019 KalVista Pharmaceuticals, Inc. KALV KVD001 Diabetic Macular Edema Phase II - Top-Line Results Late 2019 Nicox S.A. COX:FP NCX 4251 Ocular Pain and/or Inflammation Phase II Top-Line Results Late 2019 Noveome Biotherapeutics, Inc. Private ST266 Optic Neuritis Phase I - Top-Line Data Late 2019 Ocugen Inc. Private OCU310 Dry Eye Phase III - Top-Line Results Late 2019 RegeneRx Biopharmaceuticals, Inc. RGRX RGN-259 Ophthalmic Wound Healing Phase III NK - Top-Line Results Late 2019 Roivant Sciences, Inc. Private RVT-1401 Graves' Phase IIa - Top-Line Results Late 2019 Silk Tech Private SDP-4-CS201 Dry Eye Phase II - Top-Line Results Late 2019 Spark Therapeutics, Inc. ONCE SPK-7001 Congenital Blindness Phase I/II Choroideremia - Updated Results Late 2019 Sun Pharma Advanced Research Company Ltd. SPARC SDP-037 Ocular Pain and/or Inflammation Phase III - Top-Line Results Late 2019 Surface Pharmaceuticals, Inc. Private SURF-100 Dry Eye Preclinical Results Early 2020 Adverum Biotechnologies, Inc. ADVM ADVM-022 Wet AMD Phase I OPTIC - Cohort 1 Results at 52-Weeks Early 2020 Aldeyra Therapeutics, Inc. ALDX Reproxalap Dry Eye Phase III - Top-Line Results Early 2020 Aldeyra Therapeutics, Inc. ALDX ADX-2191 Other Retinopathy Phase III - Top-Line Results Early 2020 Boehringer Ingelheim GmbH Private BI 1467335 Diabetic Retinopathy Phase IIa - Top-Line Results Early 2020 Horizon Pharma plc HZNP Teprotumumab Graves' Ophthalmopathy/Orbitopathy Phase III - Updated Results Early 2020 Kodiak Sciences Inc. KOD KSI-301 Wet AMD Phase II - Top-Line Results Early 2020 Novartis AG NVS CPK850 Retinitis Pigmentosa (RP) Phase I/II - Top-Line Results Early 2020 Ocular Therapeutix, Inc. OCUL Dextenza Allergic Conjunctivitis Phase III - Top Line Trial Data Early 2020 Opthea Limited ASX: OPT OPT-302 Diabetic Macular Edema Phase IIa w/Aflibercept - Top-Line Results Early 2020 ProQR Therapeutics N.V. PRQR QRX-421a Usher Syndrome Phase I/II - Top-Line Results Early 2020 Regenera Pharma Ltd. Private RPh201 Optic Neuritis Phase III NAION - Top-Line Results Early 2020 Wize Pharma Inc. WIZP LO2A Dry Eye Phase IV - Top-Line Results Mid 2020 Biogen, Inc. BIIB BIIB111 Choroideremia Phase III STAR - Top-Line Results Mid 2020 GenSight Biologics S.A. SIGHT:FP GS010 Leber's Hereditary Optic Neuropathy Phase III REFLECT - Top-Line Results Mid 2020 Mallinckrodt plc MNK H.P. Acthar Gel Uveitis Phase IV - Top-Line Results Mid 2020 ProQR Therapeutics N.V. PRQR Sepofarsen Leber's Congenital Amaurosis Phase II/III ILLUMINATE - Top-Line Results
(1): Timing refers to the Company’s anticipated clinical readout as stated in company filings and press releases 111 Note: Includes select key top-line ophthalmology clinical events within the next twelve months Source: Company filings and Informa Market Research as of 9/30/2019 SELECT ONGOING PHASE 2 CLINICAL TRIALS
Drug Name Company Indication Target Abicipar Pegol Allergan Diabetic Macular Edema VEGF ACU-4429 Kubota Pharmaceutical Diabetic Retinopathy RPE65 ACU-4429 Kubota Pharmaceutical Stargardt Disease RPE65 AGN-199201/AGN-190584 Allergan Presbyopia Alpha Adrenergic Receptors AKST4290 Alkahest Wet AMD Eotaxin-1 / Chemokine ligand 11 ALK-001 Alkeus Pharmaceuticals Stargardt Disease Vitamin A AR-1105 Aerie Pharmaceuticals Macular Edema from Retinal Vein Occlusion Not Specified Bamosiran Sylentis Glaucoma / Ocular Hypertension Beta Adrenergic Receptors BI 1467335 Boehringer Ingelheim Diabetic Retinopathy Amine Oxidase, Copper Containing 3 CAOMECS Emmaus Life Sciences Corneal Neovascularization Stem Cells/Other Cell Therapies CBT-001 Cidara Therapeutics Pterygium Immune system CNM-Au8 Clene Nanomedicine Optic Neuritis Myelin CNTO 2476 Janssen Dry AMD / Geographic Atrophy Stem Cells/Other Cell Therapies Cyclokat Santen Pharmaceutical Dry Eye Calcineurin phosphatase DE-126 Santen Pharmaceutical Glaucoma / Ocular Hypertension Prostaglandin E Receptor 3 ECF843 Novartis Dry Eye Not Specified Elamipretide (Ophthalmic Delivery) Stealth BioTherapeutics Leber's Hereditary Optic Neuropathy Reactive Oxygen Species/Free Radicals Elamipretide (Ophthalmic Delivery) Stealth BioTherapeutics Fuchs' Corneal Endothelial Dystrophy Reactive Oxygen Species/Free Radicals Elamipretide (Systemic Delivery) Stealth BioTherapeutics Dry AMD / Geographic Atrophy Mitochondria^ Reactive Oxygen Species/Free Radicals Filgotinib Gilead Sciences Uveitis JAK/STAT GB-102 GrayBug Macular Edema from Retinal Vein Occlusion Angiogenesis^ Platelet-derived growth factor^ VEGF GB-102 GrayBug Wet AMD Angiogenesis^ Platelet-derived growth factor^ VEGF HCB1019 OcuNexus Therapeutics Dry AMD / Geographic Atrophy Connexin / Connexon / Hemichannel HCB1019 OcuNexus Therapeutics Diabetic Macular Edema Connexin / Connexon / Hemichannel HCB1019 OcuNexus Therapeutics Diabetic Retinopathy Connexin / Connexon / Hemichannel HY02 Hovione Ocular Pain and/or Inflammation Bacterial ribosome^ Gram-Negative Bacteria^ Protein synthesis ICON-1 Iconic Therapeutics Wet AMD Tissue Factor^ VEGF Inveltys Kala Pharmaceuticals Diabetic Macular Edema Glucocorticoid Receptor Inveltys Kala Pharmaceuticals Macular Edema from Retinal Vein Occlusion Glucocorticoid Receptor IONIS-FB-LRx Ionis Pharmaceuticals Dry AMD / Geographic Atrophy Complement Pathway Iscalimab Novartis Graves' Ophthalmopathy/Orbitopathy Cluster of Differentiation 40 KPI-121 0.25% Kala Pharmaceuticals Diabetic Macular Edema Glucocorticoid Receptor KPI-121 0.25% Kala Pharmaceuticals Macular Edema from Retinal Vein Occlusion Glucocorticoid Receptor KVD001 KalVista Pharmaceuticals Diabetic Macular Edema Kinin-Kallikrein System Luminate Allegro Ophthalmics Vitreomacular Adhesion Angiogenesis^ Integrins Luminate Allegro Ophthalmics Diabetic Retinopathy Angiogenesis^ Integrins Luminate Allegro Ophthalmics Diabetic Macular Edema Angiogenesis^ Integrins Mapracorat Bausch Health Dry Eye Glucocorticoid Receptor – Transrepression Selective Agonist Mapracorat Bausch Health Allergic Conjunctivitis Glucocorticoid Receptor – Transrepression Selective Agonist NCX 4251 Nicox Ocular Pain and/or Inflammation Glucocorticoid Receptor Nexagon Eyevance Pharmaceuticals Persistent Corneal Epithelial Defects Connexin / Connexon / Hemichannel Novadur Allergan Other Ophthalmological Indications Alpha 2 Adrenergic Receptor Nyxol Ocuphire Pharma Mydriasis Alpha 1 Adrenergic Receptor^ Alpha 2 Adrenergic Receptor OCS-01 Oculis Diabetic Macular Edema Unknown OCS-02 Oculis Uveitis Unknown
Note: Includes key ongoing Phase 2 clinical trials within ophthalmology indications sorted by drug name 112 Source: Company filings and ClinicalTrials.gov SELECT ONGOING PHASE 2 CLINICAL TRIALS (CONT’D)
Drug Name Company Indication Target OCS-02 Oculis Dry Eye Unknown Omaveloxolone Reata Pharmaceuticals Ocular Pain and/or Inflammation NF-Kappa B^ NRF2 Opicinumab Biogen Optic Neuritis LINGO-1 OPT-302 Opthea Wet AMD VEGF Receptor (VEGFR) Oxervate Dompé Farmaceutici Dry Eye Nerve growth factor / Trk Receptors ProDex Taiwan Liposome Macular Edema from Retinal Vein Occlusion Glucocorticoid Receptor PRT2761 Portola Pharmaceuticals Allergic Conjunctivitis Spleen Tyrosine Kinase PRX-100 Presbyopia Therapies Presbyopia Muscarinic acetylcholine receptor Renexus Neurotech Pharmaceuticals Glaucoma / Ocular Hypertension Ciliary Neurotrophic Factor Receptor Resolvine ER Kato Pharmaceuticals Diabetic Retinopathy Unknown RVT-1401 Roivant Sciences Graves' Ophthalmopathy/Orbitopathy Neonatal Fc Receptor RX-10045 Celtic Pharmaceutical Ocular Pain and/or Inflammation Immune system SDP-4 Silk Tech Dry Eye Not Specified SJP-0035 Senju Pharmaceutical Persistent Corneal Epithelial Defects Not Specified ST266 Noveome Biotherapeutics Allergic Conjunctivitis PI3K/AKT pathway^ SIRT1 ST266 Noveome Biotherapeutics Persistent Corneal Epithelial Defect PI3K/AKT pathway^ SIRT1 TB-403 BioInvent International Diabetic Macular Edema Placental growth factor Tesidolumab Novartis Ocular Pain and/or Inflammation Complement Pathway TOP1630 TopiVert Pharma Dry Eye p38 MAP kinase^ Spleen Tyrosine Kinase^ Src Kinase Family Translarna PTC Therapeutics Aniridia RNA translation Xipere Clearside Biomedical Diabetic Macular Edema Glucocorticoid Receptor Zimura Iveric Bio Polypoidal Choroidal Vasculopathy C5a Receptor^ Complement Pathway Zimura Ophthotech Dry AMD / Geographic Atrophy C5a Receptor^ Complement Pathway Zimura Iveric Bio Stargardt Disease C5a Receptor^ Complement Pathway
Note: Includes key ongoing Phase 2 clinical trials within ophthalmology indications sorted by drug name 113 Source: Company filings and ClinicalTrials.gov SELECT ONGOING PHASE 3 CLINICAL TRIALS
Drug Name Company Indication Target Beovu Novartis Diabetic Macular Edema VEGF Beovu Novartis Macular Edema from Retinal Vein Occlusion VEGF BIIB111 Biogen Choroideremia Geranylgeranyltransferase II Bimatoprost Allergan Glaucoma / Ocular Hypertension Beta Adrenergic Receptors^ Prostaglandin F receptor Blexten FAES Farma Allergic Conjunctivitis Histamine H1 Receptor Conbercept Chengdu Kanghong Biotech Wet AMD Placental growth factor^ VEGF CyclASol Novaliq Dry Eye Cyclophilin DE-117 Santen Pharmaceutical Glaucoma / Ocular Hypertension Prostaglandin E Receptor 2 DexaSite Sun Pharma Other Ophthalmological Indications Glucocorticoid Receptor Dextenza Ocular Therapeutix Allergic Conjunctivitis Glucocorticoid Receptor Eylea Regeneron Pharmaceuticals Other Retinopathy Placental growth factor^ VEGF Faricimab Roche Wet AMD Angiopoietins^ VEGF Faricimab Roche Diabetic Macular Edema Angiopoietins^ VEGF GS010 GenSight Biologics Leber's Hereditary Optic Neuropathy Mitochondrial Electron Transport Chain Hulio Mylan Uveitis Tumor Necrosis Factor-alpha Ilevro Suspension Novartis Diabetic Macular Edema Cyclooxygenases Lucentis Roche Myopic Macular Degeneration / Pathological Myopia VEGF Lucentis Roche Cystoid Macular Edema VEGF Lucentis Roche Other Retinopathy VEGF M710 Mylan Diabetic Macular Edema Placental growth factor^ VEGF Mapracorat Bausch Health Ocular Pain and/or Inflammation Glucocorticoid Receptor – Transrepression Selective Agonist MicroPine Eyenovia Myopic Macular Degeneration / Pathological Myopia Muscarinic acetylcholine receptor MicroStat Eyenovia Mydriasis Alpha 1 Adrenergic Receptor^ Muscarinic acetylcholine receptor MIM-D3 Allergan Dry Eye Nerve growth factor / Trk Receptors NVK-002 Nevakar Myopic Macular Degeneration / Pathological Myopia Not Specified OC-01 Nasal Spray Oyster Point Pharma Dry Eye Nicotinic Acetylcholine Receptors OCU310 Ocugen Dry Eye Alpha 2 Adrenergic Receptor^ Glucocorticoid Receptor Opsiria Santen Pharmaceutical Uveitis FKBP12 Optina (oral) Ampio Pharmaceuticals Diabetic Macular Edema Progesterone Receptor OTX-TP Ocular Therapeutix Glaucoma / Ocular Hypertension Prostaglandin F receptor / PGF2 alpha receptor Ozempic Novo Nordisk Diabetic Retinopathy GLP-1 Receptor PDS-1.0 Roche Wet AMD VEGF Presbysol Allergan Other Ophthalmological Indications Not Specified Renexus Neurotech Pharmaceuticals Other Congenital Blindness Indications Ciliary Neurotrophic Factor Receptor Reproxalap Aldeyra Therapeutics Allergic Conjunctivitis Aldehydes Reproxalap Aldeyra Therapeutics Dry Eye Aldehydes RGN-259 RegeneRx Biopharmaceuticals Ophthalmic Wound Healing Actin Filaments^ ATP Synthase^ Integrin-linked kinase RGN-259 RegeneRx Biopharmaceuticals Dry Eye Actin Filaments^ ATP Synthase^ Integrin-linked kinase RPh201 Regenera Pharma Optic Neuritis Unknown SDP-037 SPARC Ocular Pain and/or Inflammation Glucocorticoid Receptor SJP-0035 Senju Pharmaceutical Dry Eye Not Specified SYL1001 Sylentis Dry Eye TRPV1, transient receptor potential vanilloid receptor 1, VR-1 Visomitin Mitotech Dry Eye Mitochondria Zymar Allergan Ophthalmia Neonatorum Gram-Negative Bacteria^ Topoisomerase II and IV
Note: Includes key ongoing Phase 3 clinical trials within ophthalmology indications sorted by drug name 114 Source: Company filings and ClinicalTrials.gov Managing Director Healthcare Investment Banking [email protected] +1 (212) 293-3061 Key Market Leading Product(s) Substantial Marketed Product(s) Emerging Rx Ophthalmology Landscape (“Traditional”) Key Pipeline Product (In Clinic) Major Product(s) Under Pressure
Market Cap $1,773 $942 $782 $730 $303 $269 $218 $212 $162 $156 $129 $118 $52 $40 $38 $31 $24 $19 $15 $10 $614 $377 $157 $110 $ Millions
Ophth Focus / Med / High High Low High Low / Med High Medium Medium High High High High High High High High High High High High High Medium High High Importance
Internal Preclinical Preclinical Preclinical Allergan Wet AMD (REGN - Preclin.)
PDR & DME Preclinical Merck Preclinical
Terminated Post- NPDR Ph2
Other Retinal / Corneal Dis.
Dry AMD / GA Preclinical Preclinical
Terminated US Europe Uveitis Post-Ph3
Compounded Preclinical Valeant / B&L Glaucoma Products
Compounded Dry Eye Products
Refractive Compounded Errors Products
Conjunctivitis / Compounded Infl. / Bleph. Products
Post-Operative Compounded Pain / Infl. Products Orphan Preclinical Diseases
Ophth Gene Preclinical Preclinical Therapy
Compounding Selected Selected Private Private Companies Companies (Retina) (Front)
Source: EvaluatePharma, Biomedtracker, ClinicalTrials.gov, company materials and FactSet as of 10/18/19. Note 1: Reflects major pipeline products in clinical development and marketed products, not necessarily inclusive of all assets in development. Key Market Leading Product(s) Substantial Marketed Product(s) Emerging Rx Ophthalmology Landscape (Gene Therapy) Key Pipeline Product (In Clinic) Major Product(s) Under Pressure
Market Cap {Acq. $4B} {Acq. $854} $1,389 $516 $525 $446 $56 $38 $40 $31 $22 $7,838 $9,428 $705 $310 $2,072 $977 $572 $534 $146 $61 Prv. $ Millions
Ophth Focus / Low High Med / High Med / High Low / Med High High High High High High Low Low Low High Low Low / Med Low Low High High High Importance
Preclinical LCA (Multiple CEP290 CEP290 CEP290 RPE65 RPE65 (NR2E3, CEP290 (Preclinical) (Preclinical) (Allergan) Genes) CEP290)
LHON Preclinical MAA Planned
RPGR RPGR RPGR; RS1 XLRP (Janssen)
XLRS
Choroideremia REP-1 REP-1 Preclinical
CNGB3 / CNGA3 CNGB3 / CNGA3 Achromatopsia (Janssen)
P23H RHO P23H RHO-P23H Preclinical P23H arRP/Other RP (ProQR) (Preclinical) (Preclin, Bayer)
Stargardt’s ABCA4 Preclinical Preclinical Sanofi [Traditional] Preclinical disease (Preclinical) Neurotrophic keratopathy RegenMed (Cornea, Other)
Other IRD / Preclinical 5 PC (ND) USH2A PC (ND) PC (ND) PC (ND) Preclinical Preclinical Preclinical USH2A Preclinical Preclinical Orphan / ND (Biogen) (Regeneron) (Preclinical) (Bayer) (Novartis) (Regeneron)
Wet AMD Preclinical Preclinical
Dry AMD / GA Preclinical Roche
Glaucoma
AAV; AAV; AAV; AAV AAV AAV AAV Lentiviral AAV AAV AAV RNA RNA RNA RNA Gene Editing Gene Editing Gene Editing Gene Editing Cell Therapy Stem Cells AAV Technology Optogenetics Optogenetics Delivery
Partner(s) Novartis Roche; Biogen Janssen Sanofi Regeneron Bionic Sight Pixium Vision Regeneron Bayer Allergan Novartis Regeneron Roche (Ophth Only) (ex-US) ProQR; Biogen
Source: EvaluatePharma, Biomedtracker, ClinicalTrials.gov, company materials and FactSet as of 10/18/19. Selected Note 1: Reflects major pipeline products in clinical development and marketed products, not necessarily inclusive of all assets in Companies development. Current Equity Value
Selected Ophthalmology IPOs Since 2010
Biotechnology Specialty Pharmaceutical Gene Therapy Pre-$ Mean: $298 Pre-$ Mean: $198 Pre-$ Mean: $308 Pre -$Median: $237 Pre -$Median: $221 Pre -$Median: $336 $1,750 $4,692 $1,773 Apellis’ success stems Being acquired by Roche from their dry/wet AMD (in major part due to $1,500 potential as well as their hemophilia and broad Acquired by potential in non- platform) Biogen (driven by $1,250 ophthalmic orphan diseases IRDs and platform) $1,000 $942 $854
$730 Equity Value Equity $750 nka $599 Adverum $538 $516 $500 $446 $421 Exited $336 $348 Ophth. Exited $299 $291 $299 $318 $221 $250 $176 Ophth. $162 $119 $93 $118 $118 $57 $86 $56 $40 $24 $31 $52 $0
Ophthotech Eleven Inotek Avalanche Aerie Apellis(1) Kodiak Alimera Ocular Clearside Kala Eyenovia AGTC Spark Nightstar MeiraGTx (IVERIC) (Viventia) (Rocket) (Adverum)
Date Sep-13 Oct-13 Feb-14 Feb-15 Nov-17 Oct-18 Apr-10 Jul-14 Jun-16 Jul-17 Jan-18 Mar-14 Jul-14 Jan-15 Sep-17 Jun-18 Phase 3 Phase 2b/3 Phase 3 Phase 3 Phase 3 Phase 1 Phase 3 Phase 3 Phase 3 NDA; Ph3 Phase 3 Preclinical Phase 1/2 Phase 3 Phase 3 Phase 1/2 Phase Ongoing Preparation Preparation Preparation Preparation Ongoing Ongoing Ongoing Ongoing Prep; Ongoing Preparation Ongoing Ongoing Ongoing Preparation Ongoing Post-oper. Post-oper. P&I Choroid- Indication Wet AMD Glaucoma Dry eye Glaucoma Dry AMD Wet AMD DME ME in uveitis CACG XLRS Wet AMD RPE65 IRDs Achroma-topsia pain & infl. | dry eye eremia Proceeds $167 $67 $50 $60 $150 $90 $72 $65 $50 $104 $27 $50 $102 $161 $86 $75 Step-Up 1.5x NA 0.9x NA 2.8x 1.3x NA NA NA 1.8x NA 1.9x 2.3x 2.9x 1.8x NA
% Δ from IPO (96%) 105% (66%) (83%) 99% 98% (97%) (74%) (88%) (77%) (70%) (74%) (59%) 398% 82% (6%)
Source: FactSet and SEC filings as of 10/18/19. Note: Excludes certain companies that had non-lead ophthalmology assets at IPO, including REGENXBIO (wet AMD; IND prep), Ra Pharma (dry AMD/GA; preclinical), ProQR (LCA; preclinical), Aldeyra (uveitis; Phase 2 prep); Unity (wet AMD/diabetic retinopathy/glaucoma; preclinical); Stealth (geographic atrophy; Phase 3 prep) and others. (1) Apellis was also preparing to initiate a Ph2 study in wet AMD and was developing a SQ formulation of APL-2 for use in PNH (Ph1b ongoing) and aHUS (Ph2 planned). Step-up based on the weighted average price of the Series D and E. Rx Ophthalmology 2019YTD Stock Price Performance
In general, innovation is ruling the field in 2019 with reformulation-based companies losing steam 100%
80%
MeiraGTx 68.4% data Nightstar 60% acquisition Opthea NovaBay data Adverum Amazon 40% data distribution Spark* 29.1% acquisition 27.2% 20% 19.1%
Percent Change (%)ChangePercent 5.6% 0%
(12.8%) (20%) NASDAQ Biotech: 5.6% S&P 500: 19.1% NCE Ophth Index: 68.4% Gene Therapy Ophth Index: 27.2% Delivery/Reform Ophth Index: (12.8%) All Ophth Index: 29.1% (40%) 12/31/18 01/31/19 02/28/19 03/31/19 04/30/19 05/31/19 06/30/19 07/31/19 08/31/19 09/30/19
Source: FactSet, company websites and press releases. Data as of 10/18/19. Note: Indices are equal weighted and therefore sensitive to large swings by an individual company. Companies that had an IPO in the period are measured starting at the IPO date. NCE: Aerie; Aldeyra; Apellis; IVERIC; KalVista; Kodiak; Molecular Partners (EU); Opthea (AUS); Oxurion (EU). Gene Therapy: Adverum; AGTC; BioTime; Gensight (EU); MeiraGTx; Nightstar; ProQR; REGENXBIO*; Spark*. Delivery/Reform: Alimera; Clearside; Eyenovia; EyePoint; Harrow; Kala; Nicox (EU); NovaBay; Ocular Tx. Ophthalmology Companies by 2019YTD Stock Price Performance
Reformulation (Major Ophth Exposure) Gene Therapy (Major Ophth Exposure) Top 10 2019YTD Bottom 10 2019YTD
# Company Mkt Cap 2018 2019YTD # Company Mkt Cap 2018 2019YTD # Company Mkt Cap 2018 2019YTD
1 EyePoint $269 75% 34% 1 ReNeuron $61 (75%) 205% 1 Opthea $614 (25%) 501% 2 Eyenovia $52 (72%) 6% 2 Spark * $3,776 (24%) 193% 2 ReNeuron $61 (75%) 205% 3 Nicox $157 (53%) (8%) 3 Nightstar $854 (12%) 121% 3 Spark * $3,776 (24%) 193% 4 Harrow $129 235% (10%) 4 Adverum * $446 (10%) 120% 4 Kodiak $730 (29%) 178% 5 Ocular Tx $162 (11%) (14%) 5 MeiraGTx * $516 (36%) 46% 5 Nightstar $854 (12%) 121% 6 NovaBay $15 (80%) (20%) 6 CRISPR * $2,072 22% 33% 6 Adverum * $446 (10%) 120% 7 Clearside $31 (85%) (23%) 7 AGTC $56 (31%) 24% 7 Apellis * $1,773 (39%) 111% 8 Kala $118 (74%) (29%) 8 Lineage $146 (54%) 7% 8 MeiraGTx * $516 (36%) 46% 9 EyeGate $10 (57%) (52%) 9 REGENXBIO * $1,389 26% (10%) 9 EyePoint $269 75% 34% 10 Alimera $24 (46%) (53%) 10 Editas * $977 (26%) (13%) 10 CRISPR * $2,072 22% 33% 11 IVERIC $40 (62%) (19%) NCE (Major Ophth Exposure) Bottom 10 2019YTD 12 Intellia * $534 (29%) (20%) # Company Mkt Cap 2018 2019YTD 13 ProQR $310 389% (59%) # Company Mkt Cap 2018 2019YTD 1 Opthea $614 (25%) 501% 14 GenSight $38 (49%) (66%) 1 Aerpio $19 (64%) (73%) 2 Kodiak $730 (29%) 178% 2 Outlook $38 (62%) (67%) 3 Apellis * $1,773 (39%) 111% Ex-US Ophth (Europe, Australia, etc.) 3 GenSight $38 (49%) (66%) 4 Mol Partners $377 (28%) (9%) # Company Mkt Cap 2018 2019YTD 4 ProQR $310 389% (59%) 5 IVERIC $40 (62%) (19%) 1 Opthea $614 (25%) 501% 5 Unity * $303 (4%) (57%) 6 Oxurion $110 2% (30%) 2 ReNeuron $61 (75%) 205% 6 Alimera $24 (46%) (53%) 7 Aldeyra * $156 22% (32%) 3 Nicox $157 (53%) (8%) 7 EyeGate $10 (57%) (52%) 8 KalVista * $212 103% (40%) 4 Mol Partners $377 (28%) (9%) 8 Aerie $942 (40%) (43%) 9 Aerie $942 (40%) (43%) 5 Oxurion $110 2% (30%) 9 KalVista * $212 103% (40%) 10 Unity * $303 (4%) (57%) 6 GenSight $38 (49%) (66%) 10 Aldeyra * $156 22% (32%) 11 Outlook $38 (62%) (67%) 12 Aerpio $19 (64%) (73%)
Source: FactSet as of 10/18/19. * Denotes companies that have ex-ophthalmology drivers. Share Price Reaction to Selected ’18 & ‘19 Ophthalmology News Events
Positive Data Events in Ophthalmology (>10% Reaction & Other Selected Events) Data Event Price Reaction Performance (Around Data Event) Price Reaction (30 Days Prior to and 30 Days After Event) Company Product Indication Event Date Event +7 Days +30 Days 250% Opthea OPT-302 Wet AMD Phase 2b data Aug-19 138% 204% 318% Opthea off chart ProQR QR-110 LCA 10 Ph1/2 data Sep-18 121% 132% 126% Aldeyra Reproxalap Allergic conjunctivitis Ph3 data Mar-19 36% 22% 16% 200% Aldeyra Reproxalap Dry eye Ph2b data Sep-18 35% 27% 5% Clearside CLS-TA ME associated with uveitis Ph3 data Mar-18 32% 59% 35% 150% MeiraGTx IRD programs Achromatopsia & XLRP License to Janssen Jan-19 30% 30% 113% AGTC NITE's NSR-RPGR* XLRP Ph1/2 data Sep-18 26% 32% 27% MeiraGTx AAV-RPE65 RPE65 deficiency Ph1/2 data May-19 21% 35% 21% 100% Adverum ADVM-022 Wet AMD Updated Ph1 data @ AAO Oct-19 15% NM NM Nicox NCX 470 Glaucoma Ph2 data Oct-19 8% 0% NM 50% EyePoint Dexycu Post-operative pain Acquisition / Inv. May-18 7% 18% 13% AGTC Multiple assets XLRP & achromatopsia Ph1/2 XLRP + ACHM act. Sep-19 (0%) (16%) NM EyePoint Yutiq Uveitis Approval Oct-18 (8%) (35%) (40%) 0% Ocular Dextenza Post-operative pain Approval ? Dec-18 (14%) (12%) (41%)
(50%) (30) (20) (10) - 10 20 30
Negative Data Events in Ophthalmology (<10% Reaction & Other Selected Events) Data Event Price Reaction Price Reaction (30 Days Prior to and 30 Days After Event) Company Product Indication Event Date Event +7 Days +30 Days 60% Regenxbio RGX-314 Wet AMD Ph1 /2a data @ AAO Oct-19 (12%) ? NM NM Aldeyra Reproxalap Uveitis Phase 3 data Jun-19 (12%) (15%) (27%) 40% Aerpio AKB-9778 Drops Glaucoma Ph1 data Oct-19 (12%) NM NM Nightstar NSR-RPGR XLRP Ph1/2 data Sep-18 (16%) (28%) (57%) 20% Apellis APL-2 IVT Dry AMD / geographic atrophy Manufacturing lot Oct-18 (17%) (22%) (5%) Mol. Ptnrs Abicipar (w/ Allergan) Wet AMD Ph3 data Jul-18 (19%) (10%) (5%) 0% Gensight GS010 LHON Ph3 data #2 Feb-19 (22%) (37%) (22%) Ocular OTX-TP Post-surgical pain Ph3 data May-19 (23%) (23%) 37% (20%) Kala KPI-121 Dry eye Ph3 data Jan-18 (29%) (10%) (13%) (40%) Clearside CLS-TA DME Ph2 data May-18 (32%) (32%) (25%) AGTC XLRS program XLRS Ph2 data / Biogen term. Dec-18 (47%) (65%) (55%) (60%) Gensight GS010 LHON Ph3 data Apr-18 (48%) (45%) (48%) Adverum ADVM-022 Wet AMD Ph1 data Sep-19 (50%) (46%) NM (80%) Clearside CLS-TA RVO Ph2 data Nov-18 (63%) (71%) (77%) Aerpio AKB-9778 NPDR Ph2b data Mar-19 (71%) (77%) (75%) (100%) (30) (20) (10) - 10 20 30
Source: FactSet as of 10/18/19.